Genomes and Genes
signal transducing adaptor proteins
Summary: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
- Cotter L, Ozcelik M, Jacob C, Pereira J, Locher V, Baumann R, et al. Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination. Science. 2010;328:1415-8 pubmed publisher..Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance. ..
- Tooze S, Jefferies H, Kalie E, Longatti A, McAlpine F, McKnight N, et al. Trafficking and signaling in mammalian autophagy. IUBMB Life. 2010;62:503-8 pubmed publisher..Here, we will review the recent progress made in understanding the induction of autophagy, with emphasis on the contributions from our laboratory. ..
- Feldmann G, Mishra A, Hong S, Bisht S, Strock C, Ball D, et al. Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling. Cancer Res. 2010;70:4460-9 pubmed publisher..Conversely, restoring Ral function rescued the effects of CDK5 inhibition in pancreatic cancer cells. Our findings identify CDK5 as a pharmacologically tractable target to degrade Ras signaling in pancreatic cancer. ..
- Perrot I, Deauvieau F, Massacrier C, Hughes N, Garrone P, Durand I, et al. TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA. J Immunol. 2010;185:2080-8 pubmed publisher..Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation. ..
- Newman Z, Crown D, Leppla S, Moayeri M. Anthrax lethal toxin activates the inflammasome in sensitive rat macrophages. Biochem Biophys Res Commun. 2010;398:785-9 pubmed publisher..The activation of the rat Nlrp1 inflammasome is required for LT-mediated rat macrophage lysis and contributes to animal death. ..
- Bergamin E, Hallock P, Burden S, Hubbard S. The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization. Mol Cell. 2010;39:100-9 pubmed publisher..The structure provides the molecular basis for MuSK activation by Dok7 and for rationalizing several Dok7 loss-of-function mutations found in patients with congenital myasthenic syndromes. ..
- van der Post R, Kiemeney L, Ligtenberg M, Witjes J, Hulsbergen van de Kaa C, Bodmer D, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47:464-70 pubmed publisher..Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered. ..
- Benhamouche S, Curto M, Saotome I, Gladden A, Liu C, Giovannini M, et al. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 2010;24:1718-30 pubmed publisher..Together, our findings uncover a critical role for Nf2/Merlin in controlling homeostasis of the liver stem cell niche. ..
- Melchjorsen J, Rintahaka J, Søby S, Horan K, Poltajainen A, Østergaard L, et al. Early innate recognition of herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase III-independent pathways. J Virol. 2010;84:11350-8 pubmed publisher..Thus, innate recognition of HSV by human primary macrophages occurs via two distinct intracellular nucleotide-sensing pathways responsible for induction of IFNs and inflammatory cytokine expression, respectively. ..
- Lamason R, McCully R, Lew S, Pomerantz J. Oncogenic CARD11 mutations induce hyperactive signaling by disrupting autoinhibition by the PKC-responsive inhibitory domain. Biochemistry. 2010;49:8240-50 pubmed publisher..Our results establish a mechanism that explains how DLBCL-associated mutations in CARD11 can initiate spontaneous, receptor-independent activation of NF-?B. ..
- Zhang L, Zhang Z, Zhang X, Lin F, Ge F. Quantitative proteomics analysis reveals BAG3 as a potential target to suppress severe acute respiratory syndrome coronavirus replication. J Virol. 2010;84:6050-9 pubmed publisher..By correlating the proteomic data with these functional studies, the findings of this study provide important information for understanding SARS-CoV replication. ..
- Dubielecka P, Cui P, Xiong X, Hossain S, Heck S, Angelov L, et al. Differential regulation of macropinocytosis by Abi1/Hssh3bp1 isoforms. PLoS ONE. 2010;5:e10430 pubmed publisher..These findings also raise the possibility that isoform-specific roles occur in other Abi1 functions. ..
- Nishita M, Itsukushima S, Nomachi A, Endo M, Wang Z, Inaba D, et al. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol Cell Biol. 2010;30:3610-9 pubmed publisher..Collectively, our results indicate that Ror2/Fz receptor complex plays an important role in the Wnt5a/Rac1/AP-1 pathway by regulating the polymerization of Dvl. ..
- van Duijn T, Anthony E, Hensbergen P, Deelder A, Hordijk P. Rac1 recruits the adapter protein CMS/CD2AP to cell-cell contacts. J Biol Chem. 2010;285:20137-46 pubmed publisher..These data identify CD2AP as a novel Rac1-associated adapter protein that participates in the regulation of epithelial cell-cell contact. ..
- Pacheco V, Ma P, Thielmann Y, Hartmann R, Weiergräber O, Mohrlüder J, et al. Assessment of GABARAP self-association by its diffusion properties. J Biomol NMR. 2010;48:49-58 pubmed publisher..The possible biological significance of these observations is discussed with respect to alternative scenarios of oligomerization. ..
- Jones L, Harold D, Williams J. Genetic evidence for the involvement of lipid metabolism in Alzheimer's disease. Biochim Biophys Acta. 2010;1801:754-61 pubmed publisher..Four new genes for common AD have been revealed in the past year, CLU, CR1, PICALM and BIN1. Their possible involvement in lipid metabolism and how that relates to AD is discussed here. ..
- Zheng Y, Amin N, Hu Y, Rudrabhatla P, Shukla V, Kanungo J, et al. A 24-residue peptide (p5), derived from p35, the Cdk5 neuronal activator, specifically inhibits Cdk5-p25 hyperactivity and tau hyperphosphorylation. J Biol Chem. 2010;285:34202-12 pubmed publisher..These results suggest that p5 peptide may be a unique and useful candidate for therapeutic studies of certain neurodegenerative diseases. ..
- Würstle M, Laussmann M, Rehm M. The caspase-8 dimerization/dissociation balance is a highly potent regulator of caspase-8, -3, -6 signaling. J Biol Chem. 2010;285:33209-18 pubmed publisher..Our study therefore highlights a central and so far underappreciated role of caspase-8 dimerization/dissociation in avoiding unwanted cell death by lethal amplification of caspase responses via the caspase-8, -3, -6 loop. ..
- Levin A, Hayouka Z, Friedler A, Loyter A. Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells. Virol J. 2010;7:177 pubmed publisher..Disruption of this inhibitory complex leads to productive infection in those cells. ..
- Nicodemus K, Law A, Radulescu E, Luna A, Kolachana B, Vakkalanka R, et al. Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls. Arch Gen Psychiatry. 2010;67:991-1001 pubmed publisher..Our data suggest complex epistatic effects implicating an NRG1 molecular pathway in cognitive brain function and the pathogenesis of schizophrenia. ..
- Ramírez Valle F, Badura M, Braunstein S, Narasimhan M, Schneider R. Mitotic raptor promotes mTORC1 activity, G(2)/M cell cycle progression, and internal ribosome entry site-mediated mRNA translation. Mol Cell Biol. 2010;30:3151-64 pubmed publisher..These data suggest that this pathway may play a role in increased IRES-dependent mRNA translation during mitosis and in rapamycin insensitivity. ..
- Viiri J, Hyttinen J, Ryhanen T, Rilla K, Paimela T, Kuusisto E, et al. p62/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in human retinal pigment epithelial cells. Mol Vis. 2010;16:1399-414 pubmed..Our findings open new avenues for understanding the mechanisms of proteolytic processes in retinal cells, and could be useful in the development of novel therapies targeting p62 and HSP70. ..
- Browne C, Hoefer M, Chintalapati S, Cato M, Wallez Y, Ostertag D, et al. SHEP1 partners with CasL to promote marginal zone B-cell maturation. Proc Natl Acad Sci U S A. 2010;107:18944-9 pubmed publisher..Thus, SHEP1 orchestrates marginal zone B-cell movement and retention as a key downstream effector of the BCR and S1P receptors. ..
- Browaeys Poly E, Blanquart C, Perdereau D, Antoine A, Goenaga D, Luzy J, et al. Grb14 inhibits FGF receptor signaling through the regulation of PLC? recruitment and activation. FEBS Lett. 2010;584:4383-8 pubmed publisher..Our data led to a molecular model whereby Grb14 binding to the phosphorylated FGFR induces a conformational change that unmasks a PLC? binding motif on Grb14, allowing trapping and inactivation of PLC?. ..
- Martin J, Herbert B, Hocevar B. Disabled-2 downregulation promotes epithelial-to-mesenchymal transition. Br J Cancer. 2010;103:1716-23 pubmed publisher..Loss of Dab2 expression, commonly observed in breast cancer, may facilitate TGF?-stimulated EMT, and therefore increase the propensity for metastasis. ..
- Hitchins M. Inheritance of epigenetic aberrations (constitutional epimutations) in cancer susceptibility. Adv Genet. 2010;70:201-43 pubmed publisher..These epimutations are associated with distinct patterns of inheritance depending on the nature of the mechanisms underlying them...
- Lim M, Seo S, Kang S, Seong M, Lee B, Park S. Hereditary non-polyposis colorectal cancer/Lynch syndrome in Korean patients with endometrial cancer. Jpn J Clin Oncol. 2010;40:1121-7 pubmed publisher..2% (18 of 161)] was significant to offer genetic counseling and genetic testing in Korean endometrial cancer patients. Optimal financial support is crucial to increase the uptake rate of a genetic test. ..
- Buechler C, Wanninger J, Neumeier M. Adiponectin receptor binding proteins--recent advances in elucidating adiponectin signalling pathways. FEBS Lett. 2010;584:4280-6 pubmed publisher..This review summarizes recent studies exploiting heterologous expression of adiponectin receptors in yeast, and the type and function of the recently described adiponectin receptor associated proteins. ..
- Bolton K, Tyrer J, Song H, Ramus S, Notaridou M, Jones C, et al. Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nat Genet. 2010;42:880-4 pubmed publisher..Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development. ..
- Fendri A, Khabir A, Hadri Guiga B, Sellami Boudawara T, Daoud J, Frikha M, et al. Epigenetic alteration of the Wnt inhibitory factor-1 promoter is common and occurs in advanced stage of Tunisian nasopharyngeal carcinoma. Cancer Invest. 2010;28:896-903 pubmed publisher..003) and the age (p = .014). The Wnt-5a mRNA was higher in tumors and correlated with TNM (p = .012). The methylation of WIF-1 contributes to the activation of the Wnt pathway in NPC. ..
- Hideyama T, Yamashita T, Nishimoto Y, Suzuki T, Kwak S. Novel etiological and therapeutic strategies for neurodiseases: RNA editing enzyme abnormality in sporadic amyotrophic lateral sclerosis. J Pharmacol Sci. 2010;113:9-13 pubmed..Our review will include a discussion of new ADAR2 substrates that may be useful for research on sporadic ALS. ..
- Hammond J, McCullumsmith R, Funk A, Haroutunian V, Meador Woodruff J. Evidence for abnormal forward trafficking of AMPA receptors in frontal cortex of elderly patients with schizophrenia. Neuropsychopharmacology. 2010;35:2110-9 pubmed publisher..Together, these data suggest that there is an alteration of forward trafficking of AMPA receptors as well as changes in the subcellular localization of an AMPA receptor subunit in schizophrenia. ..
- Ossareh Nazari B, Bonizec M, Cohen M, Dokudovskaya S, Delalande F, Schaeffer C, et al. Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy. EMBO Rep. 2010;11:548-54 pubmed publisher..Our data favour the idea that these factors cooperate to recognize and deubiquitinate specific substrates of ribophagy before their vacuolar degradation. ..
- Wakabayashi N, Shin S, Slocum S, Agoston E, Wakabayashi J, Kwak M, et al. Regulation of notch1 signaling by nrf2: implications for tissue regeneration. Sci Signal. 2010;3:ra52 pubmed publisher..We report a functional role for this cross talk between the two pathways and show that disruption of Nrf2 impeded liver regeneration after partial hepatectomy and was rescued by reestablishment of Notch1 signaling. ..
- ..However, Ponpuak et al. (2010) show in this issue of Immunity that cytosolic proteins are selectively recruited to autophagosomes to become metabolized to bactericidal peptides. ..
- Gerken H, Misra R. MzrA-EnvZ interactions in the periplasm influence the EnvZ/OmpR two-component regulon. J Bacteriol. 2010;192:6271-8 pubmed publisher..Together, the data suggest that the binding of MzrA to EnvZ influences the ability of EnvZ to receive and/or respond to environmental signals in the periplasm and modulate its biochemical output to OmpR...
- Kaplan N, Tolwinski N. Spatially defined Dsh-Lgl interaction contributes to directional tissue morphogenesis. J Cell Sci. 2010;123:3157-65 pubmed publisher..We conclude that apical-basal proteins, used to establish polarity within a cell, can be independently co-opted to function in epithelial morphogenesis. ..
- Miao Y, Zhang Y, Chen Y, Chen L, Wang F. GABARAP is overexpressed in colorectal carcinoma and correlates with shortened patient survival. Hepatogastroenterology. 2010;57:257-61 pubmed..Our data demonstrated that GABARAP is frequently expressed in colorectal cancer. Overexpression of GABARAP is a new independent prognostic marker, which is associated with poor differentiation as well as shortened overall survival. ..
- Lietman S, Yin L, Levine M. SH3BP2 mutations potentiate osteoclastogenesis via PLC?. J Orthop Res. 2010;28:1425-30 pubmed publisher..The consequent activation of calcineurin and NFAT proteins induces the excessive osteoclastic phenotype of cherubism. ..
- Arnaud N, Dabo S, Maillard P, Budkowska A, Kalliampakou K, Mavromara P, et al. Hepatitis C virus controls interferon production through PKR activation. PLoS ONE. 2010;5:e10575 pubmed publisher..This opens up new possibilities to assay PKR chemical inhibitors for their potential to boost innate immunity in HCV infection. ..
- Le Clainche C, Dwivedi S, Didry D, Carlier M. Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein. J Biol Chem. 2010;285:23420-32 pubmed publisher..Finally, we show that vinculin and the formin mDia1, which is involved in the processive elongation of actin filaments in focal adhesions, compete for actin filament barbed ends. ..
- Salingcarnboriboon R, Pavasant P, Noda M. Cbl-b enhances Runx2 protein stability and augments osteocalcin promoter activity in osteoblastic cell lines. J Cell Physiol. 2010;224:743-7 pubmed publisher..Moreover, the upregulation of downstream genes of Runx2 such as osteocalcin and alkaline phosphatase mRNA was also observed. These data propose the involvement of Cbl-b in the regulation of osteoblast-related genes expression. ..
- Tanabe C, Hotoda N, Sasagawa N, Futai E, Komano H, Ishiura S. ADAM19 autolysis is activated by LPS and promotes non-classical secretion of cysteine-rich protein 2. Biochem Biophys Res Commun. 2010;396:927-32 pubmed publisher..These findings suggest that ADAM19 autolysis is activated by lipopolysaccharide and that ADAM19 promotes the secretion of CRIP2. ..
- Rondeau G, Nolet S, Latour M, Braschi S, Gaboury L, Lacroix A, et al. Clinical and biochemical features of seven adult adrenal ganglioneuromas. J Clin Endocrinol Metab. 2010;95:3118-25 pubmed publisher..We describe one of the largest series of adult adrenal GNs. Adrenal GNs may secrete testosterone or be part of a composite tumor with pheochromocytoma. The association of adrenal GN with MSH2 mutation seems to be a coincidental finding. ..
- Funasaka K, Ito S, Hasegawa H, Goldberg G, Hirooka Y, Goto H, et al. Cas utilizes Nck2 to activate Cdc42 and regulate cell polarization during cell migration in response to wound healing. FEBS J. 2010;277:3502-13 pubmed publisher..These results indicate that Cas utilizes Nck2 and CrkII in a coordinated set of distinct pathways leading to cell migration. ..
- Hofstetter B, Niemierko A, Forrer C, Benhattar J, Albertini V, Pruschy M, et al. Impact of genomic methylation on radiation sensitivity of colorectal carcinoma. Int J Radiat Oncol Biol Phys. 2010;76:1512-9 pubmed publisher..The mediators leading to sensitization remain unknown. Defining the specific factors associated with radiation sensitization after genomic demethylation may open the way to better targeting for the purpose of radiation sensitization. ..
- Scholz R, Sidler C, Thali R, Winssinger N, Cheung P, Neumann D. Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem. 2010;285:25753-66 pubmed publisher..Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation. ..
- Guezguez A, Prod homme V, Mouska X, Baudot A, Blin Wakkach C, Rottapel R, et al. 3BP2 adapter protein is required for receptor activator of NF?B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells. J Biol Chem. 2010;285:20952-63 pubmed publisher..Together, this study demonstrates that wild type 3BP2 is a key regulator of RANK-mediated macrophage differentiation into osteoclast through Src and NFATc1 activation. ..