Alfred Goldberg

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Binding of hydrophobic peptides to several non-catalytic sites promotes peptide hydrolysis by all active sites of 20 S proteasomes. Evidence for peptide-induced channel opening in the alpha-rings
    Alexei F Kisselev
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:22260-70. 2002
  2. ncbi request reprint Pathway for degradation of peptides generated by proteasomes: a key role for thimet oligopeptidase and other metallopeptidases
    Tomo Saric
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:46723-32. 2004
  3. ncbi request reprint Nobel committee tags ubiquitin for distinction
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Neuron 45:339-44. 2005
  4. pmc Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy
    Jeffrey J Brault
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:19460-71. 2010
  5. pmc Development of proteasome inhibitors as research tools and cancer drugs
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 199:583-8. 2012
  6. ncbi request reprint Protein degradation and protection against misfolded or damaged proteins
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:895-9. 2003
  7. ncbi request reprint Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy
    A L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Biochem Soc Trans 35:12-7. 2007
  8. ncbi request reprint The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Immunol 39:147-64. 2002
  9. ncbi request reprint Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate
    Alexei F Kisselev
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:8582-90. 2006
  10. ncbi request reprint ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation
    Nadia Benaroudj
    Harvard Medical School, Department of Cell Biology, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 11:69-78. 2003

Research Grants

  1. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 2004
  2. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred Goldberg; Fiscal Year: 2004
  3. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred Goldberg; Fiscal Year: 2007
  4. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2010
  5. Molecular Mechanisms that Cause Muscle Atrophy
    Alfred L Goldberg; Fiscal Year: 2010
  6. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2011
  7. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 1993
  8. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 1999
  9. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2010

Detail Information

Publications55

  1. ncbi request reprint Binding of hydrophobic peptides to several non-catalytic sites promotes peptide hydrolysis by all active sites of 20 S proteasomes. Evidence for peptide-induced channel opening in the alpha-rings
    Alexei F Kisselev
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:22260-70. 2002
    ..During protein breakdown, this peptide-induced channel opening may function to facilitate the release of products from the proteasome...
  2. ncbi request reprint Pathway for degradation of peptides generated by proteasomes: a key role for thimet oligopeptidase and other metallopeptidases
    Tomo Saric
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:46723-32. 2004
    ..Thus, degradation of most 9-17 residue proteasome products is initiated by endoproteolytic cleavages, primarily by TOP, and the resulting 6-9 residue fragments are further digested to amino acids by aminopeptidases...
  3. ncbi request reprint Nobel committee tags ubiquitin for distinction
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Neuron 45:339-44. 2005
  4. pmc Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy
    Jeffrey J Brault
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:19460-71. 2010
    ..This capacity of PGC-1alpha and PGC-1beta to inhibit FoxO3 and NFkappaB actions and proteolysis helps explain how exercise prevents muscle atrophy...
  5. pmc Development of proteasome inhibitors as research tools and cancer drugs
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 199:583-8. 2012
    ..The development of proteasome inhibitors illustrates the unpredictability, frustrations, and potential rewards of drug development but also emphasizes the dependence of medical advances on basic biological research...
  6. ncbi request reprint Protein degradation and protection against misfolded or damaged proteins
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:895-9. 2003
    ..A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded...
  7. ncbi request reprint Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy
    A L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Biochem Soc Trans 35:12-7. 2007
    ..Inhibitors of its proteolytic activity are widely used as research tools and have proven effective in cancer therapy...
  8. ncbi request reprint The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Immunol 39:147-64. 2002
    ..If cells express large amounts of TOP, class I presentation decreases, and if TOP is inhibited, presentation increases. Thus, peptide degradation in the cytosol appears to limit the efficiency of antigen presentation...
  9. ncbi request reprint Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate
    Alexei F Kisselev
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:8582-90. 2006
    ....
  10. ncbi request reprint ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation
    Nadia Benaroudj
    Harvard Medical School, Department of Cell Biology, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 11:69-78. 2003
    ..Thus, substrate binding activates ATP hydrolysis, which promotes three processes: substrate unfolding, gate opening in the 20S, and protein translocation...
  11. pmc Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes
    Paolo Cascio
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    EMBO J 21:2636-45. 2002
    ..Presumably, this change in peptides produced accounts for the capacity of PA28 to enhance antigen presentation...
  12. pmc ATP-dependent steps in the binding of ubiquitin conjugates to the 26S proteasome that commit to degradation
    Andreas Peth
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 40:671-81. 2010
    ..Unfolded or loosely folded polypeptides can inhibit this tighter binding. This commitment step precedes substrate deubiquitination and allows for selection of ubiquitinated proteins capable of being unfolded and efficiently degraded...
  13. pmc Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins
    Balasubrahmanyam Medicherla
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 182:663-73. 2008
    ..Thus, many cytosolic proteins proceed through a prolonged "fragile period" during which they are sensitive to degradation induced by superoxide radicals or increased temperatures...
  14. ncbi request reprint ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins
    David M Smith
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Mol Cell 20:687-98. 2005
    ....
  15. pmc Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis
    Xiao Bo Qiu
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 23:800-10. 2004
    ..Thus, BRUCE normally inhibits apoptosis, and Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE...
  16. ncbi request reprint The caspase-like sites of proteasomes, their substrate specificity, new inhibitors and substrates, and allosteric interactions with the trypsin-like sites
    Alexei F Kisselev
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:35869-77. 2003
    ..Thus, occupancy of the caspase-like sites stimulates the trypsin-like activity of proteasomes, but substrates of the caspase-like sites inhibit the chymotrypsin-like activity by binding to a distinct noncatalytic site...
  17. ncbi request reprint c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1
    Lei Xu
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 28:914-22. 2007
    ..Our results demonstrate that c-IAP1 exerts its oncogenic functions by promoting the degradation of an important negative regulator in the Myc pathway...
  18. pmc The ubiquitin-interacting motif protein, S5a, is ubiquitinated by all types of ubiquitin ligases by a mechanism different from typical substrate recognition
    Tomoaki Uchiki
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 284:12622-32. 2009
    ..This tendency of S5a to associate with the growing Ub chain can explain how S5a, unlike typical substrates, which are recognized by certain E3s through specific motifs, is ubiquitinated by all E3s tested and is rapidly degraded in vivo...
  19. ncbi request reprint Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
    Stewart H Lecker
    Renal Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    FASEB J 18:39-51. 2004
    ..Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases...
  20. pmc Ubiquitinated proteins activate the proteasome by binding to Usp14/Ubp6, which causes 20S gate opening
    Andreas Peth
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 36:794-804. 2009
    ..This activation enhances the selectivity of the 26S proteasome for ubiquitinated proteins and links their deubiquitination to their degradation...
  21. ncbi request reprint Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins
    Prasanna Venkatraman
    Department of Cell Biology, 240 Longwood Avenue, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 14:95-104. 2004
    ..Occasional failure of these long undegradable sequences to exit may interfere with proteasome function and help explain why longer polyQ expansions promote early disease onset...
  22. ncbi request reprint The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon, antagonizes both the precursor and mature forms of Smac and caspase-9
    Xiao Bo Qiu
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:174-82. 2005
    ..These results suggest that the ability of BRUCE to antagonize both the precursor and mature forms of Smac and caspase-9 is an important mechanism for the prevention of apoptosis under normal conditions...
  23. ncbi request reprint ATP-induced structural transitions in PAN, the proteasome-regulatory ATPase complex in Archaea
    Andrew A Horwitz
    Program in Biology and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 282:22921-9. 2007
    ..Using the protease protection maps, we modeled the conformational changes associated with ATP binding and hydrolysis in PAN based on the x-ray structures of the homologous AAA ATPase, HslU...
  24. pmc Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3
    Xiao Bo Qiu
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:14843-8. 2002
    ..These data indicate that Nrdp1 is a RING finger-type of ubiquitin ligase, which promotes degradation of ErbB3 by proteasomes and, thus, may be an important factor influencing cell growth...
  25. pmc During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation
    Shenhav Cohen
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 185:1083-95. 2009
    ..Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1...
  26. ncbi request reprint Protein degradation by the ubiquitin-proteasome pathway in normal and disease states
    Stewart H Lecker
    Nephrology Division, Beth Isreal Deaconess, Harvard Medical School, Boston, Massachusetts, USA
    J Am Soc Nephrol 17:1807-19. 2006
  27. pmc The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism
    Shih Chung Chang
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:17107-12. 2005
    ..Its "molecular ruler" mechanism involves binding the hydrophobic C terminus of the substrate 9-16 residues away from the active site...
  28. pmc Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry
    David M Smith
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 27:731-44. 2007
    ..Thus, the C termini of the proteasomal ATPases function like a "key in a lock" to induce gate opening and allow substrate entry...
  29. pmc S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains
    Hyoung Tae Kim
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 28:1867-77. 2009
    ..Thus, S5a (and presumably certain other UIM proteins) function with certain E3/E2 pairs to ensure synthesis of efficiently degraded non-forked Ub conjugates...
  30. ncbi request reprint Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages
    Hyoung Tae Kim
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:17375-86. 2007
    ....
  31. ncbi request reprint Proteasomes and their associated ATPases: a destructive combination
    David M Smith
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    J Struct Biol 156:72-83. 2006
    ..ATP therefore serves multiple functions in proteolysis and the only step that absolutely requires ATP hydrolysis is the unfolding of globular proteins. The 26S proteasome appears to function by similar mechanisms...
  32. ncbi request reprint FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells
    Jinghui Zhao
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 6:472-83. 2007
    ..These studies indicate that decreased IGF-1-PI3K-Akt signaling activates autophagy not only through mTOR but also more slowly by a transcription-dependent mechanism involving FoxO3...
  33. ncbi request reprint An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides
    Tomo Saric
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Nat Immunol 3:1169-76. 2002
    ..Like other proteins involved in antigen presentation, ERAP1 is induced by interferon-gamma. When overexpressed in vivo, we found that ERAP1 stimulates the processing and presentation of an antigenic precursor in the ER...
  34. doi request reprint Isolation of mammalian 26S proteasomes and p97/VCP complexes using the ubiquitin-like domain from HHR23B reveals novel proteasome-associated proteins
    Henrike C Besche
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 48:2538-49. 2009
    ....
  35. doi request reprint Getting to first base in proteasome assembly
    Henrike C Besche
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:25-8. 2009
    ..Recent studies have shed light on the pathway for ordered assembly of the base of the 19S regulatory particle of the 26S proteasome by identifying new precursor complexes and four dedicated chaperones involved in its assembly...
  36. ncbi request reprint Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor
    Jinghui Zhao
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Autophagy 4:378-80. 2008
    ..These findings on muscle provide the first evidence for coordinate regulation of proteasomal and lysosomal systems, although in neuronal and hepatic cells, FoxO3 stimulates the autophagic process selectively...
  37. ncbi request reprint On prions, proteasomes, and mad cows
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, USA
    N Engl J Med 357:1150-2. 2007
  38. pmc Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy
    Marco Sandri
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 117:399-412. 2004
    ..Thus, forkhead factor(s) play a critical role in the development of muscle atrophy, and inhibition of Foxo factors is an attractive approach to combat muscle wasting...
  39. ncbi request reprint Yeast adapt to near-freezing temperatures by STRE/Msn2,4-dependent induction of trehalose synthesis and certain molecular chaperones
    Olga Kandror
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 13:771-81. 2004
    ..Thus, below 10 degrees C, yeast show an adaptive response that sustains viability at low or freezing temperatures, which are commonly encountered in natural environments and laboratory refrigerators...
  40. pmc The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling
    Carsten Skurk
    Boston University School of Medicine, Whitaker Cardiovascular Institute, Boston, Massachusetts 02118, USA
    J Biol Chem 280:20814-23. 2005
    ..Thus, in cardiomyocytes, as in skeletal muscle, FOXO3a activates an atrogene transcriptional program, which retards or prevents hypertrophy and is down-regulated by multiple physiological and pathological stimuli of myocyte growth...
  41. ncbi request reprint Not just research tools--proteasome inhibitors offer therapeutic promise
    Alfred L Goldberg
    Nat Med 8:338-40. 2002
  42. ncbi request reprint IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1
    Jennifer M Sacheck
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Endocrinol Metab 287:E591-601. 2004
    ..Thus an important component of growth stimulation by IGF-I, through the PI3K-Akt pathway, is its ability to rapidly suppress transcription of the atrophy-related E3 atrogin-1 and other atrogenes and degradation of myofibrillar proteins...
  43. ncbi request reprint Post-proteasomal antigen processing for major histocompatibility complex class I presentation
    Kenneth L Rock
    Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    Nat Immunol 5:670-7. 2004
    ..Thus, the extent of antigen presentation depends on the balance between several proteolytic processes that may generate or destroy epitopes...
  44. ncbi request reprint Preparation of hybrid (19S-20S-PA28) proteasome complexes and analysis of peptides generated during protein degradation
    Paolo Cascio
    Department of Morphophysiology, School of Veterinary Medicine, University of Turin, 10095 Grugliasco, Turin, Italy
    Methods Enzymol 398:336-52. 2005
    ....
  45. ncbi request reprint Monitoring activity and inhibition of 26S proteasomes with fluorogenic peptide substrates
    Alexei F Kisselev
    Department of Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Methods Enzymol 398:364-78. 2005
    ..A novel assay of proteasome activity in crude cell extracts that allows rapid evaluation of the state of the proteasomes in cells treated with inhibitors is also described...
  46. ncbi request reprint Protein degradation and the generation of MHC class I-presented peptides
    Kenneth L Rock
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Adv Immunol 80:1-70. 2002
    ....
  47. ncbi request reprint The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation
    Ian A York
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunity 18:429-40. 2003
    ..TOP therefore plays an important role in vivo in degrading peptides released by proteasomes and is a significant factor limiting the extent of antigen presentation...
  48. ncbi request reprint New insights into the role of the ubiquitin-proteasome pathway in the regulation of apoptosis
    Cui Hua Liu
    National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing, China
    Chang Gung Med J 30:469-79. 2007
    ....
  49. ncbi request reprint Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation
    Ian A York
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 177:1434-43. 2006
    ..Moreover, these findings reveal that three sequential proteolytic steps (by proteasomes, TPPII, and then ER aminopepsidase 1) are required for the generation of a subset of epitopes...
  50. pmc hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37
    Xiao Bo Qiu
    National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 5 Dongdan Santiao, Beijing, China
    EMBO J 25:5742-53. 2006
    ..Thus in human 26S proteasomes, hRpn13 appears to be important for the binding of UCH37 to the 19S complex and for efficient proteolysis...
  51. doi request reprint Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases
    Julius Rabl
    Fachbereich Biologie, Chemie, Pharmazie, Freie Universitat Berlin, Takustrasse 3, 14195 Berlin, Germany
    Mol Cell 30:360-8. 2008
    ..This mechanism differs from that of PA26/28, which lacks the HbYX motif and does not cause alpha subunit rotation. These findings demonstrated how the ATPases' C termini function to facilitate substrate entry...
  52. ncbi request reprint The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues
    Ian A York
    Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    Nat Immunol 3:1177-84. 2002
    ..However, after interferon-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation...
  53. ncbi request reprint TNF-alpha increases ubiquitin-conjugating activity in skeletal muscle by up-regulating UbcH2/E220k
    Yi Ping Li
    Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Suite 520B, Houston, Texas 77030, USA
    FASEB J 17:1048-57. 2003
    ..Thus, UbcH2 up-regulation is a novel response to TNF-alpha/NF-kappaB signaling in skeletal muscle that appears to be essential for the increased ubiquitin conjugation induced by this cytokine...
  54. pmc Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
    Daniel J Klionsky
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Autophagy 4:151-75. 2008
    ..In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response...
  55. ncbi request reprint FoxO3 controls autophagy in skeletal muscle in vivo
    Cristina Mammucari
    Venetian Institute of Molecular Medicine, 35129 Padova, Italy
    Cell Metab 6:458-71. 2007
    ..These findings point to FoxO3 and Bnip3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved...

Research Grants36

  1. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 2004
    ..We also hope to learn more about this trimming process and about the competing pathway by which most proteasome products are digested to amino acids. ..
  2. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred Goldberg; Fiscal Year: 2004
    ..Specific Aim D will define the chaperone like function of the PAN and HslU ATPases which support protein breakdown by proteasome homologs in archeabacteria and E. coli. ..
  3. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred Goldberg; Fiscal Year: 2007
    ..We hope to learn how this disaccharide protects cell proteins against cold-induced denaturation, whether trehalose influences protein degradation, and whether higher eukaryotes show similar adaptations to near-freezing temperatures. ..
  4. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2010
    ....
  5. Molecular Mechanisms that Cause Muscle Atrophy
    Alfred L Goldberg; Fiscal Year: 2010
    ..g. cancer, sepsis, renal failure) and aging. ..
  6. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2011
    ....
  7. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 1993
    ..We also hope to elucidate the roles of ATP in their function and to learn whether these enzymes utilize similar mechanisms as the bacterial ATP-hydrolyzing proteases...
  8. MECHANISMS OF ATP-DEPENDENT PROTEOLYTIC ENZYMES
    Alfred Goldberg; Fiscal Year: 1999
    ..Finally, the project will explore the processive mechanism of the model ATP-dependent protease, La (lon), which catalyzes the rapid degradation of abnormal proteins in E. coli and mitochondria. ..
  9. MOLECULAR CHAPERONES AND PROTEIN DEGRADATION
    Alfred L Goldberg; Fiscal Year: 2010
    ..We recently found that trehalose is also required for efficient protein degradation, even in normal cells. The mechanisms of this unexpected new protective function of trehalose will be investigated. ..