Gourisankar Ghosh

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex
    Shiva Malek
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 278:23094-100. 2003
  2. ncbi request reprint Discreet mutations from c-Rel to v-Rel alter kappaB DNA recognition, IkappaBalpha binding, and dimerization: implications for v-Rel oncogenicity
    Christopher B Phelps
    Department of Chemistry and Biochemistry, University of California, San Deigo, USA
    Oncogene 23:1229-38. 2004
  3. ncbi request reprint Molecular mimicry of the NF-kappaB DNA target site by a selected RNA aptamer
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California San Diego, Mail Code 0359, Urey Hall 5230, 9500 Gilman Drive, La Jolla, CA 92093 0359, USA
    Curr Opin Struct Biol 14:21-7. 2004
  4. pmc The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes
    Olga V Savinova
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 34:591-602. 2009
  5. doi request reprint A New DNA Methyltransferase-Histone Deacetylase-Kinase Axis in Innate Immunity
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Electronic address
    Mol Cell 63:544-6. 2016
  6. doi request reprint To Swap or Not To Swap
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Electronic address
    Structure 24:1436-8. 2016
  7. pmc NF-κB potentiates caspase independent hydrogen peroxide induced cell death
    Jessica Q Ho
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 6:e16815. 2011
  8. pmc NF-κB regulation: lessons from structures
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92903, USA
    Immunol Rev 246:36-58. 2012
  9. pmc A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1
    Jacky Chi Ki Ngo
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 29:563-76. 2008
  10. ncbi request reprint Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions
    Randall Lukasiewicz
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0375, USA
    J Biol Chem 282:23036-43. 2007

Research Grants

  1. Structure/Function Studies of Nuclear FActor KB
    Gourisankar Ghosh; Fiscal Year: 2006
  2. MECHANISM OF TRANSCRIPTIONAL INHIBITION BY IKB PROTEINS
    Gourisankar Ghosh; Fiscal Year: 2002

Collaborators

Detail Information

Publications92

  1. ncbi request reprint X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex
    Shiva Malek
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 278:23094-100. 2003
    ..NF-kappaB.DNA ternary complex formation. These unique structural features of IkappaBbeta may contribute to its ability to mediate persistent NF-kappaB activation...
  2. ncbi request reprint Discreet mutations from c-Rel to v-Rel alter kappaB DNA recognition, IkappaBalpha binding, and dimerization: implications for v-Rel oncogenicity
    Christopher B Phelps
    Department of Chemistry and Biochemistry, University of California, San Deigo, USA
    Oncogene 23:1229-38. 2004
    ..We suggest that the ability of v-Rel homodimer to deregulate subunit-specific gene expression and its ability to evade IkappaB inhibition are crucial to its strong oncogenic potential...
  3. ncbi request reprint Molecular mimicry of the NF-kappaB DNA target site by a selected RNA aptamer
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California San Diego, Mail Code 0359, Urey Hall 5230, 9500 Gilman Drive, La Jolla, CA 92093 0359, USA
    Curr Opin Struct Biol 14:21-7. 2004
    ....
  4. pmc The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes
    Olga V Savinova
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 34:591-602. 2009
    ..Our biochemical evidence suggests an assembly pathway in which kinetic mechanisms control NF-kappaB dimer formation via processing and assembly of large complexes that contain IkappaB activities...
  5. doi request reprint A New DNA Methyltransferase-Histone Deacetylase-Kinase Axis in Innate Immunity
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Electronic address
    Mol Cell 63:544-6. 2016
    ..They elegantly demonstrate that DNA methylation and transcriptional activation at the HDAC9 promoter by DNMT3a, along with lysine deacetylation of TBK1 by HDAC9, are essential events during host defense. ..
  6. doi request reprint To Swap or Not To Swap
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Electronic address
    Structure 24:1436-8. 2016
    ..In this issue of Structure, Assar et al. (2016) report domain-swapped dimers of hCREBPII, pinpointing a single hydrogen bond and protein concentration as two critical regulators of the monomer/dimer balance. ..
  7. pmc NF-κB potentiates caspase independent hydrogen peroxide induced cell death
    Jessica Q Ho
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 6:e16815. 2011
    ..Although there have been a few reports addressing the pro-cell death role of NF-κB, the precise mechanism of NF-κB's pro-cell death function still remains elusive...
  8. pmc NF-κB regulation: lessons from structures
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92903, USA
    Immunol Rev 246:36-58. 2012
    ..These structures have allowed us to interpret cellular observations in molecular terms and at the same time helped us to bring forward new concepts focused towards understanding the specificity in the NF-κB activation pathway...
  9. pmc A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1
    Jacky Chi Ki Ngo
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 29:563-76. 2008
    ..We further suggest that the priming of the first serine facilitates directional substrate translocation and efficient phosphorylation...
  10. ncbi request reprint Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions
    Randall Lukasiewicz
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0375, USA
    J Biol Chem 282:23036-43. 2007
    ..Thus, there are physical attributes of SR and SR-like substrates that dictate the mechanism of phosphorylation, whereas the ability to processively phosphorylate substrates is inherent to SR protein kinases...
  11. ncbi request reprint Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty
    Adolfo Velazquez-Dones
    Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA
    J Biol Chem 280:41761-8. 2005
    ..These findings have important implications on the regulation of SR proteins in vivo by the SRPK and Clk/Sty families of kinases...
  12. pmc Adaptable molecular interactions guide phosphorylation of the SR protein ASF/SF2 by SRPK1
    Jonathan C Hagopian
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0636, USA
    J Mol Biol 382:894-909. 2008
    ..These data indicate that SRPK1 uses stable, yet highly flexible protein-protein interactions to facilitate both early and late phases of the processive phosphorylation of SR proteins...
  13. pmc NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes
    Amanda J Fusco
    Department of Chemistry and Biochemistry, University of California at San Diego, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    EMBO Rep 10:152-9. 2009
    ..We suggest that the p52:RelB heterodimer is more adaptable to complement sequence and structural variations in kappaB sites when compared with other NF-kappaB dimers...
  14. ncbi request reprint Chemical clamping allows for efficient phosphorylation of the RNA carrier protein Npl3
    Brandon E Aubol
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0506, USA
    J Biol Chem 279:30182-8. 2004
    ..The chemical clamping mechanism offers an efficient means whereby a protein kinase can simultaneously achieve both high turnover and good substrate binding properties...
  15. pmc Allosteric interactions direct binding and phosphorylation of ASF/SF2 by SRPK1
    Nhat Huynh
    Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Biochemistry 48:11432-40. 2009
    ..Thus, ASF/SF2 represents a new class of substrates that use unique primary sequence to induce allosteric binding, processive phosphorylation, and product release...
  16. ncbi request reprint Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2
    Jacky Chi Ki Ngo
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 20:77-89. 2005
    ..These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization...
  17. ncbi request reprint Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1
    Chen Ting Ma
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0636, USA
    J Mol Biol 376:55-68. 2008
    ..Taken together, these data suggest that SRPK1 uses a unique 'grab-and-pull' mechanism to control the regiospecific phosphorylation of its protein substrate...
  18. pmc Regiospecific phosphorylation control of the SR protein ASF/SF2 by SRPK1
    Chen Ting Ma
    Department of Pharmacology, University of California, La Jolla, CA 92093 0636, USA
    J Mol Biol 390:618-34. 2009
    ..Thus, while local RS/SR content steers regional preferences in the RS domain, distal contacts with SRPK1 guide initiation and directional phosphorylation within these regions...
  19. ncbi request reprint The RGG domain of Npl3p recruits Sky1p through docking interactions
    Randall Lukasiewicz
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, LaJolla, CA 92037, USA
    J Mol Biol 367:249-61. 2007
    ..We suggest that docking interaction between Sky1p and Npl3p is essential for substrate recruitment and binding specificity...
  20. pmc The IkappaBalpha/NF-kappaB complex has two hot spots, one at either end of the interface
    Simon Bergqvist
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0378, USA
    Protein Sci 17:2051-8. 2008
    ..These results suggest a "squeeze" mechanism that leads to the extremely high affinity of the IkappaBalpha*NF-kappaB complex through stabilization of the ankyrin repeat domain...
  21. pmc Stabilization of RelB requires multidomain interactions with p100/p52
    Amanda J Fusco
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
    J Biol Chem 283:12324-32. 2008
    ..This association-mediated stabilization of RelB implies a possible role for RelB in the processing of p100 into p52...
  22. ncbi request reprint Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2
    Eileen J Kennedy
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0375, USA
    J Biol Chem 283:1084-93. 2008
    ..Because many of these map outside the conserved core, this approach should be broadly useful in identifying new, more kinase-specific therapeutic targets...
  23. pmc Regulated cellular partitioning of SR protein-specific kinases in mammalian cells
    Jian Hua Ding
    Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093 0651, USA
    Mol Biol Cell 17:876-85. 2006
    ..Interestingly, a cell cycle signal induced nuclear translocation of the kinase at the G2/M boundary. These findings suggest that SRPKs may play an important role in linking signaling to RNA metabolism in higher eukaryotic cells...
  24. ncbi request reprint Novel destabilization of nucleotide binding by the gamma phosphate of ATP in the yeast SR protein kinase Sky1p
    Brandon E Aubol
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0506, USA
    Biochemistry 42:12813-20. 2003
    ..This novel finding suggests that rapid phosphoryl transfer may be facilitated by unique mechanisms in both protein kinases...
  25. ncbi request reprint SR protein kinase 1 is resilient to inactivation
    Jacky Chi Ki Ngo
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
    Structure 15:123-33. 2007
    ....
  26. pmc Interaction between the RNA binding domains of Ser-Arg splicing factor 1 and U1-70K snRNP protein determines early spliceosome assembly
    Suhyung Cho
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:8233-8. 2011
    ....
  27. ncbi request reprint Nucleotide-induced conformational changes in the Saccharomyces cerevisiae SR protein kinase, Sky1p, revealed by X-ray crystallography
    Brad Nolen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
    Biochemistry 42:9575-85. 2003
    ..Finally, we have used mutational analysis to establish the importance of a glycine within the linker that connects the two lobes of Sky1p...
  28. pmc Crystal structure of NF-kappaB (p50)2 complexed to a high-affinity RNA aptamer
    De Bin Huang
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 93092 0359, USA
    Proc Natl Acad Sci U S A 100:9268-73. 2003
    ..The structure reveals how the aptamer specifically selects p50 and discriminates against p65. We also discuss the physiological implications of RNA binding by (p50)2...
  29. pmc Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex
    Simon Bergqvist
    Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    J Mol Biol 360:421-34. 2006
    ..This could not be accounted for readily by the small loss of buried non-polar surface area and we hypothesize that the observed effect is due to additional folding of some regions of the complex...
  30. pmc Pre-folding IkappaBalpha alters control of NF-kappaB signaling
    Stephanie M E Truhlar
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    J Mol Biol 380:67-82. 2008
    ..These data demonstrate clearly that the coupled folding and binding of IkappaBalpha is critical for its precise control of NF-kappaB transcriptional activity...
  31. pmc A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation
    Smarajit Polley
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
    PLoS Biol 11:e1001581. 2013
    ..Moreover, oligomerization through the interfaces identified in this study and subsequent trans auto-phosphorylation account for the rapid amplification of IKK2 phosphorylation observed even in the absence of any upstream kinase...
  32. pmc A fourth IkappaB protein within the NF-kappaB signaling module
    Soumen Basak
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell 128:369-81. 2007
    ..Our results have important implications for physiological and pathological scenarios in which inflammatory and developmental signals converge...
  33. ncbi request reprint Crystal structure of a free kappaB DNA: insights into DNA recognition by transcription factor NF-kappaB
    De Bin Huang
    Department of Chemistry and Biochemistry, University of California, San Diego, Mail Code 0375, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    J Mol Biol 346:147-60. 2005
    ..Together, these observations suggest that NF-kappaB dimers recognize specific structural features of kappaB DNA in order to make sequence-specific complexes...
  34. pmc A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation
    Shomyseh Sanjabi
    Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095 1662, USA
    Genes Dev 19:2138-51. 2005
    ....
  35. pmc NF-kappaB dictates the degradation pathway of IkappaBalpha
    Erika Mathes
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0375, USA
    EMBO J 27:1357-67. 2008
    ..In addition, we find that both free and bound IkappaBalpha are similar substrates for IKK, and the preferential phosphorylation of NF-kappaB-bound IkappaBalpha is due to stabilization of IkappaBalpha by NF-kappaB...
  36. pmc X-ray structure of a NF-kappaB p50/RelB/DNA complex reveals assembly of multiple dimers on tandem kappaB sites
    Anu K Moorthy
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    J Mol Biol 373:723-34. 2007
    ..We suggest that multiple NF-kappaB dimers assemble at diverse kappaB promoters through direct interactions utilizing unique protein-protein interaction surfaces...
  37. pmc The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements
    Vivien Ya Fan Wang
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cell Rep 2:824-39. 2012
    ..Therefore, through sensing of bp differences within κB sites, NF-κB dimers modulate biological programs by activating, repressing, and altering the expression of effector genes...
  38. pmc Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones
    Xiang Yang Zhong
    Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 23:482-95. 2009
    ....
  39. pmc Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha
    Simon Bergqvist
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093 0378, USA
    Proc Natl Acad Sci U S A 106:19328-33. 2009
    ..Mutational stabilization of these repeats reduces the efficiency with which IkappaBalpha enhances the dissociation rate...
  40. pmc Contribution of non-catalytic core residues to activity and regulation in protein kinase A
    Jie Yang
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 284:6241-8. 2009
    ..The study exemplifies two different ways for regulating cAMP-dependent protein kinase activity through non-conserved residues and sheds light on the structural and functional diversity of the kinase family...
  41. pmc Inhibition of NF-kappaB activity by IkappaBbeta in association with kappaB-Ras
    Yi Chen
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, USA
    Mol Cell Biol 24:3048-56. 2004
    ..We suggest that specific signals, in addition to those that activate only IKK, are essential for the complete degradation of IkappaBbeta...
  42. pmc Probing kinase activation and substrate specificity with an engineered monomeric IKK2
    Arthur V Hauenstein
    Structural Biochemistry Laboratory, Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182 1030, United States
    Biochemistry 53:2064-73. 2014
    ....
  43. pmc The SRSF1 linker induces semi-conservative ESE binding by cooperating with the RRMs
    Suhyung Cho
    Department of Chemistry and Biochemistry, University of California, San Diego 9500 Gilman Drive, La Jolla, CA 92093, USA
    Nucleic Acids Res 39:9413-21. 2011
    ....
  44. pmc Identifying critical non-catalytic residues that modulate protein kinase A activity
    Eileen J Kennedy
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 4:e4746. 2009
    ..Kinase misregulation has been directly linked to a variety of cancers, underscoring the necessity for understanding intramolecular kinase regulation...
  45. pmc A structural guide to proteins of the NF-kappaB signaling module
    Tom Huxford
    Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182 1030, USA
    Cold Spring Harb Perspect Biol 1:a000075. 2009
    ..Studies aimed at characterizing the molecular mechanisms of NF-kappaB, IkappaB, and IKK in terms of their three-dimensional structures have lead to a greater understanding of this vital transcription factor system...
  46. pmc Mechanism of dephosphorylation of the SR protein ASF/SF2 by protein phosphatase 1
    Chen Ting Ma
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0636, USA
    J Mol Biol 403:386-404. 2010
    ..The data indicate that both RNA-protein interactions and phosphorylation in flanking sequences induce conformations of ASF/SF2 that increase the lifetime of phosphates in the RS domain...
  47. ncbi request reprint Solvent exposed non-contacting amino acids play a critical role in NF-kappaB/IkappaBalpha complex formation
    Tom Huxford
    Department of Chemistry and Biochemistry, University of California at San Diego, Mail Code 0359, 9500 Gilman Drive, La Jolla, CA 92093 0359, USA
    J Mol Biol 324:587-97. 2002
    ..X-ray crystallographic and solvent accessibility experiments suggest that these solvent-exposed amino acid residues contribute to NF-kappaB/IkappaBalpha complex formation by modulating the NF-kappaB p65 subunit NLS polypeptide...
  48. pmc Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription
    Sulakshana P Mukherjee
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, United States of America Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS Biol 11:e1001647. 2013
    ..Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a possible role of CBP/p300 in recruitment of RelA to its target promoter sites...
  49. pmc Kinetic control of negative feedback regulators of NF-kappaB/RelA determines their pathogen- and cytokine-receptor signaling specificity
    Vincent F S Shih
    Signaling Systems Laboratory and Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0375, USA
    Proc Natl Acad Sci U S A 106:9619-24. 2009
    ..Finally, we found that IkappaB delta provides signaling memory owing to its long half-life; it integrates the inflammatory history of the cell to dampen NF-kappaB responsiveness during sequential stimulation events...
  50. pmc IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer
    Rachel Tsui
    1 Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M C 0375, La Jolla, California, 92093 0375 2 The San Diego Center for Systems Biology, University of California, San Diego, 9500 Gilman Dr M C 0375, La Jolla, California, 92093 0375 3 Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M C 0375, La Jolla, California, 92093 0375
    Nat Commun 6:7068. 2015
    ....
  51. pmc Processive phosphorylation of alternative splicing factor/splicing factor 2
    Brandon E Aubol
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0506, USA
    Proc Natl Acad Sci U S A 100:12601-6. 2003
    ..These data demonstrate that SRPK1 phosphorylates a specific region within the RS domain of ASF/SF2 by using a fully processive catalytic mechanism, in which the splicing factor remains "locked" onto SRPK1 during RS domain modification...
  52. pmc The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation-independent manner
    Anu K Moorthy
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, 92093, USA
    EMBO J 25:1945-56. 2006
    ..This suggests that the GRR impedes the complete degradation of the p105 precursor, thus contributing to p50 generation...
  53. pmc NEMO ensures signaling specificity of the pleiotropic IKKβ by directing its kinase activity toward IκBα
    Bärbel Schröfelbauer
    Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    Mol Cell 47:111-21. 2012
    ..Our work establishes a role for scaffolds such as NEMO in determining stimulus-specific signal transduction via the pleiotropic signaling hub IKK...
  54. ncbi request reprint NF-kappaB RelB forms an intertwined homodimer
    De Bin Huang
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Structure 13:1365-73. 2005
    ..We show that, as in the crystal, RelB forms an intertwined homodimer in solution. We suggest that the transiently stable RelB homodimer might prevent its rapid degradation, allowing for heterodimer formation with p50 and p52...
  55. pmc Flexible regions within I{kappa}B{alpha} create the ubiquitin-independent degradation signal
    Erika Mathes
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 285:32927-36. 2010
    ..Both the C-terminal and 5th ankyrin repeat degradation signals have inherent flexibility and specific hydrophobic residue(s), which together constitute the ubiquitin-independent degradation signal for IκBα...
  56. pmc p100/IκBδ sequesters and inhibits NF-κB through kappaBsome formation
    Zhihua Tao
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093
    Proc Natl Acad Sci U S A 111:15946-51. 2014
    ....
  57. ncbi request reprint Regulation of protein kinases; controlling activity through activation segment conformation
    Brad Nolen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92116, USA
    Mol Cell 15:661-75. 2004
    ..Here we examine these structures using a structural bioinformatics approach to understand how the conformation of the activation segment controls kinase activity...
  58. ncbi request reprint PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking
    Susan S Taylor
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093, USA
    Cell 122:823-5. 2005
    ..The structures, coupled with mutagenesis analysis, also demonstrate how phosphorylation of the activation loop can allosterically couple two distal regions, the dimerization and substrate recognition interfaces...
  59. pmc The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50
    Christine S Cheng
    Signaling Systems Laboratory, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Sci Signal 4:ra11. 2011
    ....
  60. pmc N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation
    Brandon E Aubol
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0636, U S A
    Biochem J 462:143-52. 2014
    ..These findings suggest that CLK1-dependent hyperphosphorylation is the result of a general mechanism in which the N-terminus acts as a bridge connecting the kinase domain and the RS domain of the SR protein. ..
  61. pmc Pho5p and newly identified nucleotide pyrophosphatases/ phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae
    Eileen J Kennedy
    Department of Chemistry and Biochemistry, and UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093 0347, USA
    Eukaryot Cell 4:1892-901. 2005
    ..This study demonstrates that extracellular nucleotide phosphate metabolism appears to be controlled by at least two independent regulatory mechanisms, uniting phosphate starvation with extracellular nucleotide regulation...
  62. doi request reprint A structural basis for selective dimerization by NF-κB RelB
    Don Vu
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    J Mol Biol 425:1934-45. 2013
    ..We suggest that RelB has evolved into a specialized NF-κB subunit with unique amino acids optimized for selective formation of heterodimers with p50 and p52...
  63. pmc Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers
    Giuseppina Bonizzi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    EMBO J 23:4202-10. 2004
    ..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway...
  64. ncbi request reprint KappaB-Ras binds to the unique insert within the ankyrin repeat domain of IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta x NF-kappaB complexes
    Yi Chen
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 278:23101-6. 2003
    ..NF-kappaB complexes can reside in the nucleus...
  65. ncbi request reprint Mechanistic insights into Sky1p, a yeast homologue of the mammalian SR protein kinases
    Brandon E Aubol
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
    Biochemistry 41:10002-9. 2002
    ..These studies represent the first kinetic investigation of a member of the SRPK family and the first pre-steady-state kinetic study of a protein kinase using a natural protein substrate...
  66. ncbi request reprint Inhibitor kappaB kinase beta binding by inhibitor kappaB kinase gamma
    Devin Drew
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Biochemistry 46:12482-90. 2007
    ..We also found that the IKKbeta C-terminal domain formed a dimer in solution and the basic unit of the IKKbeta/IKKgamma complex was a dimer/dimer...
  67. pmc Phosphorylation mechanism and structure of serine-arginine protein kinases
    Gourisankar Ghosh
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA
    FEBS J 278:587-97. 2011
    ..These studies indicate that efficient regiospecific phosphorylation of SRSF1 is the result of a contoured binding cavity in SRPK1, a lengthy Arg-Ser repetitive segment in the RS domain, and a highly directional processing mechanism...
  68. doi request reprint Understanding the logic of IκB:NF-κB regulation in structural terms
    Tom Huxford
    Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182 1030, USA
    Curr Top Microbiol Immunol 349:1-24. 2011
    ..Here we provide a detailed description of these fundamental NF-κB regulatory events using as a basis macromolecular structures and experimental data derived from structure-based biochemistry...
  69. pmc Attenuation of yeast UPR is essential for survival and is mediated by IRE1 kinase
    Aditi Chawla
    Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 193:41-50. 2011
    ..We propose that the activity of the Ire1 kinase domain plays a role in attenuating its RNase activity when ER function is recovered...
  70. pmc Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution
    Carrie Hughes Croy
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    Protein Sci 13:1767-77. 2004
    ..The ramifications of these observations for the biological function of IkappaBalpha are discussed...
  71. pmc Crosstalk via the NF-kappaB signaling system
    Soumen Basak
    Department of Chemistry and Biochemistry, Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States
    Cytokine Growth Factor Rev 19:187-97. 2008
    ..We argue that a systems approach will be valuable for understanding questions of specificity and emergent properties of highly networked cellular signaling systems...
  72. ncbi request reprint Circuitry of nuclear factor kappaB signaling
    Alexander Hoffmann
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
    Immunol Rev 210:171-86. 2006
    ..Understanding the genetic regulatory circuitry of NF-kappaB functionalities involves system-wide measurements, biophysical studies, and computational modeling...
  73. ncbi request reprint p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B
    Anu K Moorthy
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 278:556-66. 2003
    ..We speculate that additional cytoplasmic protein(s) may sequester the entire p105.NF-kappaB complex by binding through the death domain and other segments, including the exposed NLS...
  74. ncbi request reprint Inhibition of transcription factor NF-kappaB activation by kappaB-Ras
    Tom Huxford
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA
    Methods Enzymol 407:527-34. 2006
    ....
  75. ncbi request reprint The kappa B DNA sequence from the HIV long terminal repeat functions as an allosteric regulator of HIV transcription
    Frances E Chen-Park
    Department of Biology, University of California, San Diego, La Jolla, California 92093 0359, USA
    J Biol Chem 277:24701-8. 2002
    ..These functional differences correlate with observed conformational differences and demonstrate that distinct kappaB DNA sequences function as allosteric regulators in a gene-specific manner...
  76. ncbi request reprint Inflammatory tales of liver cancer
    Alexander Hoffmann
    Signaling Systems Laboratory, University of California, San Diego, La Jolla, CA 92093, USA
    Cancer Cell 11:99-101. 2007
    ..These studies suggest careful examination of NF-kappaB inhibitors as a therapeutic modality for cancer...
  77. pmc IkappaBepsilon provides negative feedback to control NF-kappaB oscillations, signaling dynamics, and inflammatory gene expression
    Jeffrey D Kearns
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
    J Cell Biol 173:659-64. 2006
    ....
  78. pmc The regulatory logic of the NF-kappaB signaling system
    Ellen O'Dea
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
    Cold Spring Harb Perspect Biol 2:a000216. 2010
    ..We discuss the prevailing mechanisms that mediate signaling cross talk...
  79. pmc UV as an amplifier rather than inducer of NF-kappaB activity
    Ellen L O'Dea
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    Mol Cell 30:632-41. 2008
    ..Our work suggests that the human health relevance of NF-kappaB activation by UV lies with cellular homeostatic states that are associated with pathology rather than with healthy physiology...
  80. pmc Defective regulation of CXCR2 facilitates neutrophil release from bone marrow causing spontaneous inflammation in severely NF-kappa B-deficient mice
    Sibylle von Vietinghoff
    Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92122, USA
    J Immunol 185:670-8. 2010
    ..These neutrophil effects may limit the usefulness of global NF-kappaB inhibitors for the treatment of inflammatory diseases...
  81. pmc Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system
    Soumen Basak
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0375, USA
    Mol Cell Biol 28:3139-50. 2008
    ..Our results inform a wiring diagram to delineate NF-kappaB dimer formation that emphasizes that inflammatory and developmental signaling cannot be considered separately but are highly interconnected...
  82. ncbi request reprint Cutting edge: innate immunity conferred by B cells is regulated by caspase-8
    Daniel R Beisner
    Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
    J Immunol 175:3469-73. 2005
    ..The activation of NF-kappaB or IFN regulatory factor 3 was found to be unaffected by the loss of caspase-8, implicating it in a novel pathway important for some forms of innate immunity mediated by B cells...
  83. ncbi request reprint Stimulus specificity of gene expression programs determined by temporal control of IKK activity
    Shannon L Werner
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, 9500 Gilman Drive, Mailcode 0375, La Jolla, CA 92093 0375, USA
    Science 309:1857-61. 2005
    ..Thus, the distinct biological responses to LPS and TNFalpha depend on signaling pathway-specific mechanisms that regulate the temporal profile of IKK activity...
  84. ncbi request reprint Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulators
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
    Immunity 23:319-29. 2005
    ..Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival...
  85. pmc Encoding NF-kappaB temporal control in response to TNF: distinct roles for the negative regulators IkappaBalpha and A20
    Shannon L Werner
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 22:2093-101. 2008
    ..Our results delineate the nonredundant functions implied by the knockout phenotypes of ikappabalpha and a20, and identify the latter as a signaling cross-talk mediator controlling inflammatory and developmental responses...
  86. pmc A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity
    Ellen L O'Dea
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, UCSD, La Jolla, CA 92037, USA
    Mol Syst Biol 3:111. 2007
    ....
  87. pmc Comment on "Oscillations in NF-kappaB signaling control the dynamics of gene expression"
    Derren Barken
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry and Bioinformatics Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    Science 308:52; author reply 52. 2005
  88. pmc NF-κB signaling
    Ellen O'Dea
    Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA
    Wiley Interdiscip Rev Syst Biol Med 1:107-15. 2009
    ..In addition, we summarize the evidence for cross-talk mechanisms that allow for different stimuli to be integrated within the NF-κB signaling module to produce synergistic or qualitatively different signaling outcomes...
  89. pmc Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
    Sumito Ogawa
    Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Cell 122:707-21. 2005
    ..These findings reveal combinatorial control of homeostasis and immune responses by nuclear receptors and suggest new approaches for treatment of inflammatory diseases...
  90. ncbi request reprint CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV Response
    Tomohisa Kato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Mol Cell 12:829-39. 2003
    ..Inhibition of this pathway prevents UV-induced IkappaBalpha degradation and increases UV-induced cell death. Thus, the p38-CK2-NF-kappaB axis is an important component of the mammalian UV response...
  91. ncbi request reprint Enhanced intracellular mobility and nuclear accumulation of DNA plasmids associated with a karyophilic protein
    Adi Mesika
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Hum Gene Ther 16:200-8. 2005
    ..Facilitated transport of p50-DNA complexes in the cytoplasm proceeded along microtubules in a dynein-dependent manner and is mediated by the heterodimeric nuclear transport receptor that recognizes the p50-born NLS...
  92. ncbi request reprint The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the interferon beta -kappa B site
    Benjamin Berkowitz
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA
    J Biol Chem 277:24694-700. 2002
    ..The precise molecular mechanism behind the involvement of the high mobility group protein I(Y) in interferon beta enhanceosome formation remains elusive...

Research Grants2

  1. Structure/Function Studies of Nuclear FActor KB
    Gourisankar Ghosh; Fiscal Year: 2006
    ..We hope that the proposed biochemical work will be helpful for better biological understanding of NF-kB as well as in developing useful small molecule drugs for anti inflammatory reactions. ..
  2. MECHANISM OF TRANSCRIPTIONAL INHIBITION BY IKB PROTEINS
    Gourisankar Ghosh; Fiscal Year: 2002
    ..These experiments will allow us to propose a model for how different complex formation between Rel/NFkappaB and IkappaB ultimately dictates the fate of a specific cell type. ..