Genomes and Genes
Summary: Macromolecular complexes formed from the association of defined protein subunits.
- Zhang J, Kim J, Alexander A, Cai S, Tripathi D, Dere R, et al. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nat Cell Biol. 2013;15:1186-96 pubmed publisher..These data identify a role for the TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signalling organelle involved in regulation of mTORC1. ..
- Yamamoto R, Song K, Yanagisawa H, Fox L, Yagi T, Wirschell M, et al. The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility. J Cell Biol. 2013;201:263-78 pubmed publisher..The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility...
- Dibble C, Manning B. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol. 2013;15:555-64 pubmed publisher..Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology. ..
- Knyazev D, Lents A, Krause E, Ollinger N, Siligan C, Papinski D, et al. The bacterial translocon SecYEG opens upon ribosome binding. J Biol Chem. 2013;288:17941-6 pubmed publisher..Thus, the open probability of the channel must be close to unity. To prevent the otherwise lethal proton leak, a closed post-translational conformation of the SecYEG complex bound to a ribosome must exist...
- Das J, Chakraborty S, Podder S, Ghosh T. Complex-forming proteins escape the robust regulations of miRNA in human. FEBS Lett. 2013;587:2284-7 pubmed publisher..However, the duplicated complex-forming proteins having a severe effect on organismal fitness are profoundly targeted by miRNA, probably to reduce the chances of dosage imbalance. ..
- Petit C, Roczniak Ferguson A, Ferguson S. Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases. J Cell Biol. 2013;202:1107-22 pubmed publisher..These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid-dependent activation of mTOR via its direct interaction with the RagA/B GTPases. ..
- Wang Q, Tiffen J, Bailey C, Lehman M, Ritchie W, Fazli L, et al. Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development. J Natl Cancer Inst. 2013;105:1463-73 pubmed publisher..Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes. ..
- Humphrey S, Yang G, Yang P, Fazakerley D, Stöckli J, Yang J, et al. Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2. Cell Metab. 2013;17:1009-20 pubmed publisher..The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists. ..
- Demetriades C, Doumpas N, Teleman A. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell. 2014;156:786-99 pubmed publisher..These data suggest that regulation of TSC2 subcellular localization may be a general mechanism to control its activity and place TSC2 in the amino-acid-sensing pathway to TORC1...
- Tsun Z, Bar Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell. 2013;52:495-505 pubmed publisher..We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a molecular function for the FLCN tumor suppressor. ..
- Naito T, Kuma A, Mizushima N. Differential contribution of insulin and amino acids to the mTORC1-autophagy pathway in the liver and muscle. J Biol Chem. 2013;288:21074-81 pubmed publisher..These results suggest that autophagy is differentially regulated by insulin and amino acids in a tissue-dependent manner. ..
- Chen C, Kiyan V, Zhylkibayev A, Kazyken D, Bulgakova O, Page K, et al. Autoregulation of the mechanistic target of rapamycin (mTOR) complex 2 integrity is controlled by an ATP-dependent mechanism. J Biol Chem. 2013;288:27019-30 pubmed publisher..Thus, the homeostatic ATP sensor mTOR controls the integrity of mTORC2 and phosphorylation of Akt on the turn motif site. ..
- Graham S, Wartosch L, Gray S, Scourfield E, Deane J, Luzio J, et al. Structural basis of Vps33A recruitment to the human HOPS complex by Vps16. Proc Natl Acad Sci U S A. 2013;110:13345-50 pubmed publisher..The Vps33A-Vps16 complex provides a structural framework for studying the association between Sec1/Munc18 proteins and tethering complexes. ..
- Marsh J, Hern ndez H, Hall Z, Ahnert S, Perica T, Robinson C, et al. Protein complexes are under evolutionary selection to assemble via ordered pathways. Cell. 2013;153:461-70 pubmed publisher..Together, these results reveal the intimate relationships among protein assembly, quaternary structure, and evolution and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways...
- Klinger C, Klute M, Dacks J. Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa. PLoS ONE. 2013;8:e76278 pubmed publisher..Overall, we demonstrate reduction of MTCs in Apicomplexa and their ancestors, consistent with modification during, and possibly pre-dating, the move from free-living marine algae to deadly human parasites...
- Taylor P. Role of amino acid transporters in amino acid sensing. Am J Clin Nutr. 2014;99:223S-230S pubmed publisher..New opportunities for nutritional therapy may include targeting of AA transporters (or mechanisms that upregulate their expression) to promote protein-anabolic signals for retention or recovery of lean tissue mass. ..
- Balderhaar H, Ungermann C. CORVET and HOPS tethering complexes - coordinators of endosome and lysosome fusion. J Cell Sci. 2013;126:1307-16 pubmed publisher..Here, we discuss the general function of both complexes in yeast and in metazoan cells in the context of endosomal biogenesis and maturation...
- Fernández Cid A, Riera A, Tognetti S, Herrera M, Samel S, Evrin C, et al. An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly. Mol Cell. 2013;50:577-88 pubmed publisher..Importantly, CDK-dependent phosphorylation of ORC inhibits OCM establishment to ensure once per cell cycle replication. In summary, this work reveals multiple critical mechanisms that redefine our understanding of DNA licensing. ..
- Thedieck K, Holzwarth B, Prentzell M, Boehlke C, Kläsener K, Ruf S, et al. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells. Cell. 2013;154:859-74 pubmed publisher..Importantly, we show that in cancer cells, apoptosis suppression during stress depends on astrin. Being frequently upregulated in tumors, astrin is a potential clinically relevant target to sensitize tumors to apoptosis. ..
- Buster D, Daniel S, Nguyen H, Windler S, Skwarek L, Peterson M, et al. SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2. J Cell Biol. 2013;201:49-63 pubmed publisher..Therefore, SCF(Slimb)-mediated down-regulation of condensin II is required to maintain proper organization and morphology of the interphase nucleus. ..
- Betz C, Stracka D, Prescianotto Baschong C, Frieden M, Demaurex N, Hall M. Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci U S A. 2013;110:12526-34 pubmed publisher..Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and metabolism. ..
- Linares J, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz Meco M. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell. 2013;51:283-96 pubmed publisher..Interfering with the p62-TRAF6 interaction serves to modulate autophagy and nutrient sensing. ..
- Wauson E, Lorente Rodríguez A, Cobb M. Minireview: Nutrient sensing by G protein-coupled receptors. Mol Endocrinol. 2013;27:1188-97 pubmed publisher..This review focuses on an array of findings on sensing amino acids and sweet molecules outside of neurons by this cluster of class C GPCRs and some of the physiologic processes regulated by them. ..
- Weber T, Koob S, Heide H, Wittig I, Head B, VAN DER BLIEK A, et al. APOOL is a cardiolipin-binding constituent of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria. PLoS ONE. 2013;8:e63683 pubmed publisher..Our findings further assign an intracellular role to a member of the apolipoprotein family in mammals. ..
- Castets P, Lin S, Rion N, Di Fulvio S, Romanino K, Guridi M, et al. Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy. Cell Metab. 2013;17:731-44 pubmed publisher..These findings may open interesting avenues for therapeutic strategies directed toward autophagy-related muscle diseases. ..
- Das R, Melo J, Thondamal M, Morton E, Cornwell A, Crick B, et al. The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans. PLoS Genet. 2017;13:e1007038 pubmed publisher..HPK-1 therefore provides a promising intervention point for pharmacological agents targeting the protein homeostasis system as a means of preserving robust longevity. ..
- Hu J, Che L, Li L, Pilo M, Cigliano A, Ribback S, et al. Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. Sci Rep. 2016;6:20484 pubmed publisher..Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades. ..
- Chen D, Huang Y, Ruan Y, Shen W. The evolutionary landscape of PRC1 core components in green lineage. Planta. 2016;243:825-46 pubmed publisher..Plant LHP1 as the homolog of non-PRC1 protein HP1 was recruited to fulfill the role of Pc counterpart. Gene duplication followed by functional divergence makes a great contribution to evolutionary progress of PRC1 in green plants. ..
- Kim K, Qiang L, Hayden M, Sparling D, Purcell N, Pajvani U. mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun. 2016;7:10255 pubmed publisher..These data suggest that the balance of free and mTORC1-associated Raptor governs hepatic lipid accumulation, and uncover the potentially therapeutic role of PHLPP2 activators in non-alcoholic fatty liver disease. ..
- Mahmoud S, Planes M, Cabedo M, Trujillo C, Rienzo A, Caballero Molada M, et al. TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis. FEBS Lett. 2017;591:1993-2002 pubmed publisher..Tco89 does not affect Pma1 activity but activates K+ transport. ..
- Singleton M. Getting to the heart of an unusual kinetochore. Open Biol. 2016;6:160040 pubmed publisher..Two recent studies provide new structural insights into the formation of this complex, and highlight some intriguing adaptations found in the Drosophila kinetochore. ..
- Moreno J, Miranda Azpiazu P, GarcÃa Bea A, Younkin J, Cui M, Kozlenkov A, et al. Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. Sci Signal. 2016;9:ra5 pubmed publisherHeterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors...
- Montavon T, Kwon Y, Zimmermann A, Hammann P, Vincent T, Cognat V, et al. A specific dsRNA-binding protein complex selectively sequesters endogenous inverted-repeat siRNA precursors and inhibits their processing. Nucleic Acids Res. 2017;45:1330-1344 pubmed publisher..The existence of such a complex and its implication regarding the still elusive biological function of plant endoIR-siRNA will be discussed. ..
- Deng Y, Asbury C. Simultaneous Manipulation and Super-Resolution Fluorescence Imaging of Individual Kinetochores Coupled to Microtubule Tips. Methods Mol Biol. 2017;1486:437-467 pubmed publisherKinetochores are large multiprotein complexes that drive mitotic chromosome movements by mechanically coupling them to the growing and shortening tips of spindle microtubules...
- Makowski M, Willems E, Jansen P, Vermeulen M. Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin-associated Protein Complexes Using Single Affinity Purification. Mol Cell Proteomics. 2016;15:854-65 pubmed publisher..This work, therefore, demonstrates that xIP-MS is a robust, flexible, and widely applicable methodology for interrogating chromatin-associated protein complex architectures. ..
- Chen Z, Morales J, Guerrero P, Sun H, McCarty J. PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells. Cancer Res. 2018;78:3809-3822 pubmed publisher..protein (Vcp), an ATP-dependent protein segregase that selectively extracts ubiquitinated proteins from multiprotein complexes and targets them for degradation via the ubiquitin proteasome system...
- Ye X, Zhou Q, Matsumoto Y, Moriyama M, Kageyama S, Komatsu M, et al. Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma. Anticancer Res. 2016;36:6021-6029 pubmed..Targeting glutaminolysis may represent a potential therapeutic strategy for the treatment of Gln-dependent lung squamous cell carcinomas. ..
- Tran L, Basdevant N, PrÃ©vost C, Ha Duong T. Structure of ring-shaped AÎ²â‚„â‚‚ oligomers determined by conformational selection. Sci Rep. 2016;6:21429 pubmed publisher..In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of AÎ² peptide self-assembly. ..
- Engel C, Gubbey T, Neyer S, Sainsbury S, Oberthuer C, Baejen C, et al. Structural Basis of RNA Polymerase I Transcription Initiation. Cell. 2017;169:120-131.e22 pubmed publisher..Comparison with the Pol II system suggests that promoter specificity relies on a distinct "bendability" and "meltability" of the promoter sequence that enables contacts between initiation factors, DNA, and polymerase. ..
- Ding B, Zhong Q. Zinc deficiency: An unexpected trigger for autophagy. J Biol Chem. 2017;292:8531-8532 pubmed publisher..A recent study shows that, in yeast, zinc depletion acts in a similar fashion. Depletion of this essential nutrient induces non-selective autophagy by inhibiting TORC1, leading to release and recycling of zinc from degraded proteins. ..
- ..In their recent study, Yin et al. show that mTOR can regulate signaling through the insulin-like growth factor 1 receptor and that it possesses a new enzymatic activity - the ability to phosphorylate proteins on tyrosine residues. ..
- Eiseler T, Wille C, Koehler C, Illing A, Seufferlein T. Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion. J Biol Chem. 2016;291:462-77 pubmed publisher..In conclusion, our data indicate that PKD2 is a core factor in the formation of this multiprotein complex at the TGN that controls constitutive secretion of matrix metalloproteinase cargo. ..
- Drew K, Lee C, Huizar R, Tu F, Borgeson B, McWhite C, et al. Integration of over 9,000 mass spectrometry experiments builds a global map of human proteinÂ complexes. Mol Syst Biol. 2017;13:932 pubmed publisher..MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease. ..
- Spiller M, Guo L, Wang Q, Tran P, Lu H. Mitochondrial Tim9 protects Tim10 from degradation by the protease Yme1. Biosci Rep. 2015;35: pubmed publisher..We propose that Tim10, rather than the hexameric Tim9-Tim10 complex, is the functional form of these proteins. ..
- Buszewicz D, Archacki R, Palusiński A, Kotlinski M, Fogtman A, Iwanicka Nowicka R, et al. HD2C histone deacetylase and a SWI/SNF chromatin remodelling complex interact and both are involved in mediating the heat stress response in Arabidopsis. Plant Cell Environ. 2016;39:2108-22 pubmed publisherStudies in yeast and animals have revealed that histone deacetylases (HDACs) often act as components of multiprotein complexes, including chromatin remodelling complexes (CRCs)...
- Wang J, Blevins T, Podicheti R, Haag J, Tan E, Wang F, et al. Mutation of Arabidopsis SMC4 identifies condensin as a corepressor of pericentromeric transposons and conditionally expressed genes. Genes Dev. 2017;31:1601-1614 pubmed publisher..Collectively, our genome-wide analyses implicate condensin in the suppression of hundreds of loci, acting in both DNA methylation-dependent and methylation-independent pathways. ..
- Ramachandran S, Osterhaus S, Parekh K, Jacobi A, Behlke M, McCray P. SYVN1, NEDD8, and FBXO2 Proteins Regulate ?F508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation. J Biol Chem. 2016;291:25489-25504 pubmed..It suggests that SYVN1 and FBXO2 represent two distinct multiprotein complexes that may degrade ?F508-CFTR in airway epithelia and identifies a new role for NEDD8 in regulating ?F508-..