Genomes and Genes
Experts and Doctors on multiprotein complexes in Ann Arbor, Michigan, United States
Locale: Ann Arbor, Michigan, United States
Topic: multiprotein complexes
- Murga Zamalloa C, Swaroop A, Khanna H. Multiprotein complexes of Retinitis Pigmentosa GTPase regulator (RPGR), a ciliary protein mutated in X-linked Retinitis Pigmentosa (XLRP). Adv Exp Med Biol. 2010;664:105-14 pubmed publisher..Piecing together the RPGR-interactome in different subcellular compartments should provide critical insights into the role of alternative RPGR isoforms in associated orphan and syndromic retinal degenerative diseases. ..
- Hurd T, Fan S, Margolis B. Localization of retinitis pigmentosa 2 to cilia is regulated by Importin beta2. J Cell Sci. 2011;124:718-26 pubmed publisher..Together, this work further highlights a role of Importin ?2 in regulation of the entry of RP2 and other proteins into the ciliary compartment. ..
- Bridges D, Ma J, Park S, Inoki K, Weisman L, Saltiel A. Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1. Mol Biol Cell. 2012;23:2955-62 pubmed publisher..Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P(2). Together these results suggest that PI(3,5)P(2) is an essential mTORC1 regulator that defines the localization of the complex. ..
- BEMBENEK J, Verbrugghe K, Khanikar J, Csankovszki G, Chan R. Condensin and the spindle midzone prevent cytokinesis failure induced by chromatin bridges in C. elegans embryos. Curr Biol. 2013;23:937-46 pubmed publisher..We postulate that condensin I is recruited by Aurora B(AIR-2) to aid in the resolution of chromatin obstructions and also helps generate a signal to maintain the delay in cytokinesis...
- Pacitto R, Gaeta I, Swanson J, Yoshida S. CXCL12-induced macropinocytosis modulates two distinct pathways to activate mTORC1 in macrophages. J Leukoc Biol. 2017;101:683-692 pubmed publisher..These results indicate that CXCL12 activates mTORC1 via 2 mechanisms: 1) that the macropinocytic cup localizes Akt signaling and 2) that MPs convey extracellular nutrients to lysosomes. ..
- Brace E, Parkinson L, Fuller R. Skp1p regulates Soi3p/Rav1p association with endosomal membranes but is not required for vacuolar ATPase assembly. Eukaryot Cell. 2006;5:2104-13 pubmed..This work also provides a generalizable approach to defining the roles of interactions of Skp1p with individual F-box proteins through the isolation of special alleles of SKP1. ..
- Thomsen A, Plouffe B, Cahill T, Shukla A, Tarrasch J, Dosey A, et al. GPCR-G Protein-?-Arrestin Super-Complex Mediates Sustained G Protein Signaling. Cell. 2016;166:907-919 pubmed publisher..The formation of such megaplexes provides a potential physical basis for the newly appreciated sustained G protein signaling from internalized GPCRs. ..
- Couture J, Collazo E, Trievel R. Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol. 2006;13:698-703 pubmed
- Wu D, Topper L, Wilson T. Recruitment and dissociation of nonhomologous end joining proteins at a DNA double-strand break in Saccharomyces cerevisiae. Genetics. 2008;178:1237-49 pubmed publisher..These findings reveal the in vivo assembly of the NHEJ repair complex and shed light on the mechanisms controlling DSB repair pathway utilization. ..
- Pierchala B, Muñoz M, Tsui C. Proteomic analysis of the slit diaphragm complex: CLIC5 is a protein critical for podocyte morphology and function. Kidney Int. 2010;78:868-82 pubmed publisher..Thus, our study identifies CLIC5 as a new component that is enriched in and necessary for foot process integrity and podocyte function in vivo. ..
- Roca H, Varsos Z, Pienta K. CCL2 is a negative regulator of AMP-activated protein kinase to sustain mTOR complex-1 activation, survivin expression, and cell survival in human prostate cancer PC3 cells. Neoplasia. 2009;11:1309-17 pubmed..Altogether, these findings suggest that CCL2 hyperactivates mTORC1 through simultaneous regulation of both AMPK and Akt pathways and reveals a new network that promotes prostate cancer: CCL2-AMPK-mTORC1-survivin. ..
- Nakada D, Saunders T, Morrison S. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature. 2010;468:653-8 pubmed publisher..Lkb1 is therefore required for HSC maintenance through AMPK-dependent and AMPK-independent mechanisms, revealing differences in metabolic and cell-cycle regulation between HSCs and some other haematopoietic progenitors. ..
- Collette K, Petty E, Golenberg N, BEMBENEK J, Csankovszki G. Different roles for Aurora B in condensin targeting during mitosis and meiosis. J Cell Sci. 2011;124:3684-94 pubmed publisher..By contrast, during meiosis, AIR-2 is not required for condensin I chromosomal association, but it provides cues for correct spatial targeting of the complex. ..
- Klionsky D, Codogno P. The mechanism and physiological function of macroautophagy. J Innate Immun. 2013;5:427-33 pubmed publisher..Indeed, defects in autophagy are associated with many human diseases and metabolic disorders. Here, we provide a brief overview of the mechanism of autophagy and some of the physiological roles in which this process is involved. ..
- D Andrea Merrins M, Chang L, Lam A, Ernst S, Stuenkel E. Munc18c interaction with syntaxin 4 monomers and SNARE complex intermediates in GLUT4 vesicle trafficking. J Biol Chem. 2007;282:16553-66 pubmed..Therefore, in contradiction to previous models, our data indicates that the conformational "opening" of syntaxin 4 rather than the dissociation of Munc18c is the critical event required for GLUT4 vesicle docking. ..
- Ikenoue T, Inoki K, Yang Q, Zhou X, Guan K. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008;27:1919-31 pubmed publisher..Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation. ..
- Yang Q, Inoki K, Kim E, Guan K. TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc Natl Acad Sci U S A. 2006;103:6811-6 pubmed..Our observations suggest that TSC1/2 and Rheb have different effects on the activity of TORC1 and -2, further supporting the complexity of TOR regulation. ..
- Han L, Hyung S, Mayers J, Ruotolo B. Bound anions differentially stabilize multiprotein complexes in the absence of bulk solvent. J Am Chem Soc. 2011;133:11358-67 pubmed publisher..Anion-resolved data acquired for smaller protein systems allows us to classify anions into three categories based on their ability to stabilize protein and protein complex structure in the absence of bulk solvent...
- Braun D, Rao J, Mollet G, Schapiro D, Daugeron M, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49:1529-1538 pubmed publisher..We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. ..
- Foster K, Acosta Jaquez H, Romeo Y, Ekim B, Soliman G, Carriere A, et al. Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. J Biol Chem. 2010;285:80-94 pubmed publisher..Taken together, these data suggest that complex raptor phosphorylation functions as a biochemical rheostat that modulates mTORC1 signaling in accordance with environmental cues. ..
- Inoki K. Role of TSC-mTOR pathway in diabetic nephropathy. Diabetes Res Clin Pract. 2008;82 Suppl 1:S59-62 pubmed publisher..Dysregulation of the TSC-mTOR pathway may cause not only tumor development but also metabolic disorders such as diabetes and its complications. ..
- Murga Zamalloa C, Desai N, Hildebrandt F, Khanna H. Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas. Mol Vis. 2010;16:1373-81 pubmed..RPGR may regulate some complexes with NPHP proteins in the mammalian retina. The disruption of these complexes may contribute to the pathogenesis of retinal degeneration in X-linked RP and associated ciliary diseases. ..
- Ward J, Vasu K, Deutschman E, Halawani D, Larson P, Zhang D, et al. Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells. PLoS Genet. 2017;13:e1007051 pubmed publisher..These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells. ..
- Muñoz Planillo R, Franchi L, Miller L, Nunez G. A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J Immunol. 2009;183:3942-8 pubmed publisher..Furthermore, these studies revealed that hemolysins promote in the presence of lipoproteins the activation of the Nlrp3 inflammasome. ..
- Crozier S, Sans M, Wang J, Lentz S, Ernst S, Williams J. CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth. Am J Physiol Gastrointest Liver Physiol. 2010;299:G1154-63 pubmed publisher..Prolonged mTORC1 activation is thus required for dietary protein-induced pancreatic growth in the absence of CCK...
- Roca H, Varsos Z, Mizutani K, Pienta K. CCL2, survivin and autophagy: new links with implications in human cancer. Autophagy. 2008;4:969-71 pubmed..How these life or death decisions are regulated remains unclear. Here we discuss the function of survivin in the control of autophagy and the interaction between CCL2, survivin and autophagy in the complex program of tumor progression. ..
- Li X, Wu L, Corsa C, Kunkel S, Dou Y. Two mammalian MOF complexes regulate transcription activation by distinct mechanisms. Mol Cell. 2009;36:290-301 pubmed publisher..Our results support a model that these two MOF complexes regulate distinct stages of transcription activation in cooperation with other histone modifying activities. ..
- Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest. 2011;121:2181-96 pubmed publisher..These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN. ..
- Lamanna A, Karbstein K. Nob1 binds the single-stranded cleavage site D at the 3'-end of 18S rRNA with its PIN domain. Proc Natl Acad Sci U S A. 2009;106:14259-64 pubmed publisher..Using these results, we have built a model for Nob1's interaction with preribosomes. ..
- Brackenbury W, Calhoun J, Chen C, Miyazaki H, Nukina N, Oyama F, et al. Functional reciprocity between Na+ channel Nav1.6 and beta1 subunits in the coordinated regulation of excitability and neurite outgrowth. Proc Natl Acad Sci U S A. 2010;107:2283-8 pubmed publisher..6 localization and consequent high-frequency firing require beta1. We conclude that VGSC subunits function in macromolecular signaling complexes regulating both neuronal excitability and migration during cerebellar development. ..
- Wang F, Podell E, Zaug A, Yang Y, Baciu P, Cech T, et al. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007;445:506-10 pubmed..We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension. ..
- Rauch J, Gestwicki J. Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70) generates functionally distinct complexes in vitro. J Biol Chem. 2014;289:1402-14 pubmed publisher..Given the number and diversity of cochaperones in mammals, it is likely that combinatorial assembly could generate a large number of distinct permutations. ..
- Sun S, Chen S, Liu F, Wu H, McHugh J, Bergin I, et al. Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling. Cancer Cell. 2015;28:758-772 pubmed publisher..These studies demonstrated critical mechanisms of aberrant mTORC1 activation in lymphangiosarcoma and validate the mice as a valuable model for further study. ..
- Gummow B, Scheys J, Cancelli V, Hammer G. Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex. Mol Endocrinol. 2006;20:2711-23 pubmed..These data indicate that GR provides feedback regulation of adrenocortical steroid production through synergistic activation of Dax-1 with SF-1, which is antagonized by ACTH activation of the adrenal cortex...
- Bridges D, Fisher K, Zolov S, Xiong T, Inoki K, Weisman L, et al. Rab5 proteins regulate activation and localization of target of rapamycin complex 1. J Biol Chem. 2012;287:20913-21 pubmed publisher..Additionally, regulation of PI(3)P synthesis by Rab5 and Vps21 is essential for TORC1 function in both contexts. ..
- Villanueva E, Munzberg H, Cota D, Leshan R, Kopp K, Ishida Takahashi R, et al. Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status. Endocrinology. 2009;150:4541-51 pubmed publisher..The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations. ..
- Venkatareddy M, Cook L, Abuarquob K, Verma R, Garg P. Nephrin regulates lamellipodia formation by assembling a protein complex that includes Ship2, filamin and lamellipodin. PLoS ONE. 2011;6:e28710 pubmed publisher..These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics. ..
- Margolis B, Borg J. Apicobasal polarity complexes. J Cell Sci. 2005;118:5157-9 pubmed
- Zhang T, Li Y, Yu Y, Zou P, Jiang Y, Sun D. Characterization of celastrol to inhibit hsp90 and cdc37 interaction. J Biol Chem. 2009;284:35381-9 pubmed publisher..These data suggest that celastrol may represent a new class of Hsp90 inhibitor by modifying Hsp90 C terminus to allosterically regulate its chaperone activity and disrupt Hsp90-Cdc37 complex. ..
- Yoshida S, Hong S, Suzuki T, Nada S, Mannan A, Wang J, et al. Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway. J Biol Chem. 2011;286:32651-60 pubmed publisher..Taken together, our results suggest that the TSC complex plays an important role in redox-sensitive mTORC1 regulation and argues for the activation of mTORC1 in places other than the lysosome upon inhibition of the TSC complex. ..
- Backues S, Lynch Day M, Klionsky D. The Ume6-Sin3-Rpd3 complex regulates ATG8 transcription to control autophagosome size. Autophagy. 2012;8:1835-6 pubmed publisher..However, many of the ATG genes show some level of transcriptional induction upon starvation. Now, we show that transcription of ATG8 is repressed under growing conditions by the Ume6-Sin3-Rpd3 complex. ..
- Zhong H, Bryson A, Eckersdorff M, Ferguson D. Rad50 depletion impacts upon ATR-dependent DNA damage responses. Hum Mol Genet. 2005;14:2685-93 pubmed..These studies contribute to our understanding of the central role that MRN plays in damage detection and signaling, which serve to maintain genomic stability and resist neoplastic transformation. ..
- Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan K. Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol Cell Biol. 1999;19:5523-34 pubmed..Together, these results suggest that KSR may act as a scaffolding protein for the Ras-mitogen-activated protein kinase pathway. ..
- Gururaj C, Federman R, Federman R, Chang A. Orm proteins integrate multiple signals to maintain sphingolipid homeostasis. J Biol Chem. 2013;288:20453-63 pubmed publisher..Conversely, the calcium- and calcineurin-dependent pathway signals ER stress response upon lipid dysregulation in the absence of the Orm proteins to restore ER homeostasis. ..
- Legakis J, Yen W, Klionsky D. A cycling protein complex required for selective autophagy. Autophagy. 2007;3:422-32 pubmed
- Csomos R, Wright C, Galban S, Oetjen K, Duckett C. Two distinct signalling cascades target the NF-kappaB regulatory factor c-IAP1 for degradation. Biochem J. 2009;420:83-91 pubmed publisher..Thus c-IAP1 can be targeted for degradation by two distinct processes, revealing the critical importance of this molecule as a regulator of numerous intracellular signalling cascades. ..
- Ahuja S, Jahr N, Im S, Vivekanandan S, Popovych N, Le Clair S, et al. A model of the membrane-bound cytochrome b5-cytochrome P450 complex from NMR and mutagenesis data. J Biol Chem. 2013;288:22080-95 pubmed publisher..We have also shown that the addition of a substrate to cytP450 likely strengthens the cytb5-cytP450 interaction. This study paves the way to obtaining valuable structural, functional, and dynamic information on membrane-bound complexes...
- Perkey E, Fingar D, Miller R, Garcia G. Increased mammalian target of rapamycin complex 2 signaling promotes age-related decline in CD4 T cell signaling and function. J Immunol. 2013;191:4648-55 pubmed publisher..The data presented in this article suggest a novel model in which aging increases TORC2 signaling and leads to CD4 T cell defects in old mice. ..
- Reimer T, Shaw M, Franchi L, Coban C, Ishii K, Akira S, et al. Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome. Eur J Immunol. 2010;40:764-9 pubmed publisher..These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL-1 receptor pathway. ..
- Zeng Z, Wang W, Yang Y, Chen Y, Yang X, Diehl J, et al. Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Dev Cell. 2010;18:214-25 pubmed publisher..Our results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control. ..
- Mao K, Chew L, Inoue Aono Y, Cheong H, Nair U, Popelka H, et al. Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation. Proc Natl Acad Sci U S A. 2013;110:E2875-84 pubmed publisher..Finally, single-particle electron microscopy analysis of the Atg17-Atg31-Atg29 complex reveals an elongated structure with Atg29 located at the opposing ends. ..
- Palaniappan M, Menon B, Menon K. Stimulatory effect of insulin on theca-interstitial cell proliferation and cell cycle regulatory proteins through MTORC1 dependent pathway. Mol Cell Endocrinol. 2013;366:81-9 pubmed publisher..Taken together, the present studies show that insulin stimulates cell proliferation and cell cycle regulatory proteins in T-I cells via activation of the MTORC1 signaling pathway. ..
- Csankovszki G. Condensin function in dosage compensation. Epigenetics. 2009;4:212-5 pubmed..We discuss how during worm dosage compensation a condensin-mediated function may guide the organization of the interphase chromatin fibers, leading to the formation of a repressive nuclear compartment. ..
- Inoki K, Guan K. Complexity of the TOR signaling network. Trends Cell Biol. 2006;16:206-12 pubmed..Here, we discuss new findings that have extended the complexity of TOR signaling and the different roles of the TORC complexes in yeast, flies and mammals. ..
- Harder J, Franchi L, Muñoz Planillo R, Park J, Reimer T, Nunez G. Activation of the Nlrp3 inflammasome by Streptococcus pyogenes requires streptolysin O and NF-kappa B activation but proceeds independently of TLR signaling and P2X7 receptor. J Immunol. 2009;183:5823-9 pubmed publisher..pyogenes peritoneal infection. These results indicate that caspase-1 activation in response to S. pyogenes infection requires NF-kappaB and the virulence factor streptolysin O, but proceeds independently of P2X7R and TLR signaling. ..