Khdrbs1

Summary

Gene Symbol: Khdrbs1
Description: KH domain containing, RNA binding, signal transduction associated 1
Alias: Sam68, p62, p68, KH domain-containing, RNA-binding, signal transduction-associated protein 1, GAP-associated tyrosine phosphoprotein p62, khdrbs1, p21 Ras GTPase-activating protein-associated p62, src associated in mitosis, 68 kDa, src-associated in mitosis 68 kDa protein
Species: mouse
Products:     Khdrbs1

Top Publications

  1. Chawla G, Lin C, Han A, Shiue L, Ares M, Black D. Sam68 regulates a set of alternatively spliced exons during neurogenesis. Mol Cell Biol. 2009;29:201-13 pubmed publisher
    b>Sam68 (Src-associated in mitosis, 68 kDa) is a KH domain RNA binding protein implicated in a variety of cellular processes, including alternative pre-mRNA splicing, but its functions are not well understood...
  2. Klein M, Younts T, Castillo P, Jordan B. RNA-binding protein Sam68 controls synapse number and local ?-actin mRNA metabolism in dendrites. Proc Natl Acad Sci U S A. 2013;110:3125-30 pubmed publisher
    ..Functional loss of the 68-kDa RBP Src associated in mitosis (Sam68) is associated with the pathogenesis of the neurological disorder fragile X tremor/ataxia syndrome...
  3. Matter N, Herrlich P, König H. Signal-dependent regulation of splicing via phosphorylation of Sam68. Nature. 2002;420:691-5 pubmed
    ..We show that the nuclear RNA-binding protein Sam68 is a new extracellular signal-regulated kinase (ERK) target...
  4. Paronetto M, Zalfa F, Botti F, Geremia R, Bagni C, Sette C. The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes. Mol Biol Cell. 2006;17:14-24 pubmed
    ..Herein we have investigated the expression and function during mammalian male meiosis of Sam68, an RNA-binding protein implicated in several aspects of RNA metabolism...
  5. Paronetto M, Messina V, Barchi M, Geremia R, Richard S, Sette C. Sam68 marks the transcriptionally active stages of spermatogenesis and modulates alternative splicing in male germ cells. Nucleic Acids Res. 2011;39:4961-74 pubmed publisher
    b>Sam68 plays an essential role in mouse spermatogenesis and male fertility. Herein, we report an interaction between Sam68 and the phosphorylated forms of the RNA polymerase II (RNAPII) in meiotic spermatocytes...
  6. Richard S, Vogel G, Huot M, Guo T, Muller W, Lukong K. Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis. Oncogene. 2008;27:548-56 pubmed
    The Src-associated substrate in mitosis Sam68 is a KH type RNA-binding protein known to be a substrate of numerous tyrosine kinases, and often referred to as a STAR (signal transduction activator of RNA) protein...
  7. Iijima T, Wu K, Witte H, Hanno Iijima Y, Glatter T, Richard S, et al. SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1. Cell. 2011;147:1601-14 pubmed publisher
    ..Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA-binding protein SAM68 that associates with RNA response elements in the Nrxn1 pre-mRNA...
  8. Lukong K, Richard S. Motor coordination defects in mice deficient for the Sam68 RNA-binding protein. Behav Brain Res. 2008;189:357-63 pubmed publisher
    ..We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in ..
  9. Fumagalli S, Totty N, Hsuan J, Courtneidge S. A target for Src in mitosis. Nature. 1994;368:871-4 pubmed
    ..Purification and microsequencing of p68 showed that it was related to the previously described GAP-associated protein p62 (ref. 6).

More Information

Publications58

  1. Di Fruscio M, Chen T, Richard S. Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis. Proc Natl Acad Sci U S A. 1999;96:2710-5 pubmed
    b>Sam68, the 68-kDa Src substrate associated during mitosis, is an RNA-binding protein with signaling properties that contains a GSG (GRP33, Sam68, GLD-1) domain...
  2. Hong W, Resnick R, Rakowski C, Shalloway D, Taylor S, Blobel G. Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68. Mol Cancer Res. 2002;1:48-55 pubmed
    ..We identified the Src substrate and RNA-binding protein Sam68 as novel CH3-binding protein...
  3. Richard S, Yu D, Blumer K, Hausladen D, Olszowy M, Connelly P, et al. Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1. Mol Cell Biol. 1995;15:186-97 pubmed
    ..By using the yeast two-hybrid system, we identified p62, a tyrosine-phosphorylated protein that associates with p21ras GTPase-activating protein, as a src family kinase ..
  4. Rajan P, Dalgliesh C, Bourgeois C, Heiner M, Emami K, Clark E, et al. Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies. BMC Cell Biol. 2009;10:82 pubmed publisher
    ..b>Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA)..
  5. Paronetto M, Messina V, Bianchi E, Barchi M, Vogel G, Moretti C, et al. Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. J Cell Biol. 2009;185:235-49 pubmed publisher
    b>Sam68 is a KH-type RNA-binding protein involved in several steps of RNA metabolism with potential implications in cell differentiation and cancer. However, its physiological roles are still poorly understood...
  6. Richard S, Torabi N, Franco G, Tremblay G, Chen T, Vogel G, et al. Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss. PLoS Genet. 2005;1:e74 pubmed
    The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive...
  7. Lukong K, Richard S. Sam68, the KH domain-containing superSTAR. Biochim Biophys Acta. 2003;1653:73-86 pubmed
    b>Sam68 is one of the most studied members of the STAR family of RNA-binding proteins since its identification over a decade ago...
  8. Bianchi E, Barbagallo F, Valeri C, Geremia R, Salustri A, De Felici M, et al. Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. Hum Mol Genet. 2010;19:4886-94 pubmed publisher
    b>Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads, whose ablation causes male infertility. Herein, we have investigated Sam68 expression in the adult ovary and its function in female fertility...
  9. Sette C, Messina V, Paronetto M. Sam68: a new STAR in the male fertility firmament. J Androl. 2010;31:66-74 pubmed publisher
    ..Recent evidence indicates that the RNA-binding protein Sam68 is absolutely required for the correct progression of spermatogenesis and for male fertility in the mouse...
  10. Wong G, Muller O, Clark R, Conroy L, Moran M, Polakis P, et al. Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62. Cell. 1992;69:551-8 pubmed
    b>p62 is a tyrosine phosphoprotein that associates with p21ras GTPase-activating protein (GAP). Purification and cDNA cloning of p62 reveal extensive sequence similarity to a putative hnRNP protein, GRP33...
  11. Fu K, Sun X, Wier E, Hodgson A, Liu Y, Sears C, et al. Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-?B activation. elife. 2016;5: pubmed publisher
    ..domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-?B regulator in genotoxic stress-initiated signaling pathway...
  12. Vernet C, Artzt K. STAR, a gene family involved in signal transduction and activation of RNA. Trends Genet. 1997;13:479-84 pubmed
    ..It is hypothesized that these bifunctional proteins provide a rich source of interesting molecular information about development and define a new cellular pathway that links signal transduction directly to RNA metabolism. ..
  13. Chen T, Damaj B, Herrera C, Lasko P, Richard S. Self-association of the single-KH-domain family members Sam68, GRP33, GLD-1, and Qk1: role of the KH domain. Mol Cell Biol. 1997;17:5707-18 pubmed
    b>Sam68 is a member of a growing family of proteins that contain a single KH domain embedded in a larger conserved domain of approximately 170 amino acids...
  14. Tomalka J, de Jesus T, Ramakrishnan P. Sam68 is a regulator of Toll-like receptor signaling. Cell Mol Immunol. 2017;14:107-117 pubmed publisher
    ..We identified Sam68 as a novel regulator of TLR-induced NF-?B and MAPK activation...
  15. Funakoshi Tago M, Tago K, Andoh K, Sonoda Y, Tominaga S, Kasahara T. Functional role of c-Src in IL-1-induced NF-kappa B activation: c-Src is a component of the IKK complex. J Biochem. 2005;137:189-97 pubmed
    ..Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-kappa B activation through the IKK complex. ..
  16. Arron J, Vologodskaia M, Wong B, Naramura M, Kim N, Gu H, et al. A positive regulatory role for Cbl family proteins in tumor necrosis factor-related activation-induced cytokine (trance) and CD40L-mediated Akt activation. J Biol Chem. 2001;276:30011-7 pubmed
    ..These findings implicate Cbl family proteins as not only negative regulators of signaling but as positive modulators of TNF receptor superfamily signaling as well. ..
  17. Tremblay G, Richard S. mRNAs associated with the Sam68 RNA binding protein. RNA Biol. 2006;3:90-3 pubmed
    The Src associated substrate in mitosis of 68kDa, Sam68, is an RNA-binding protein that belongs to the KH domain family of proteins...
  18. Iijima T, Iijima Y, Witte H, Scheiffele P. Neuronal cell type-specific alternative splicing is regulated by the KH domain protein SLM1. J Cell Biol. 2014;204:331-42 pubmed publisher
    ..Thus, cell type-specific expression of SLM1 provides a mechanism for shaping the molecular repertoires of synaptic adhesion molecules in neuronal populations in vivo...
  19. Haegebarth A, Heap D, Bie W, Derry J, Richard S, Tyner A. The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2. J Biol Chem. 2004;279:54398-404 pubmed
    ..Only a few substrates have been identified for BRK/Sik, including the KH domain containing RNA-binding protein Sam68 and the novel adaptor protein BKS...
  20. Zhou J, Cheng M, Boriboun C, Ardehali M, Jiang C, Liu Q, et al. Inhibition of Sam68 triggers adipose tissue browning. J Endocrinol. 2015;225:181-9 pubmed publisher
    ..Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity...
  21. La Rosa P, Bielli P, Compagnucci C, Cesari E, Volpe E, Farioli Vecchioli S, et al. Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing. elife. 2016;5: pubmed publisher
    ..We found that the RNA- binding protein Sam68 (Khdrbs1) is strongly expressed in neurogenic areas of the neocortex and supports the self-renewing potential of mouse ..
  22. Huot M, Brown C, Lamarche Vane N, Richard S. An adaptor role for cytoplasmic Sam68 in modulating Src activity during cell polarization. Mol Cell Biol. 2009;29:1933-43 pubmed publisher
    The Src-associated substrate during mitosis with a molecular mass of 68 kDa (Sam68) is predominantly nuclear and is known to associate with proteins containing the Src homology 3 (SH3) and SH2 domains...
  23. Derry J, Prins G, Ray V, Tyner A. Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene. 2003;22:4212-20 pubmed
    ..However localization of Sam68, a nuclear substrate of BRK/Sik, was unaltered in all prostate tumors examined...
  24. Ramakrishnan P, Baltimore D. Sam68 is required for both NF-?B activation and apoptosis signaling by the TNF receptor. Mol Cell. 2011;43:167-79 pubmed publisher
    The RNA-binding protein Sam68 is implicated in various cellular processes including RNA metabolism, apoptosis, and signal transduction. Here we identify a role of Sam68 in TNF-induced NF-?B activation and apoptosis...
  25. Vogel G, Richard S. Emerging roles for Sam68 in adipogenesis and neuronal development. RNA Biol. 2012;9:1129-33 pubmed publisher
    b>Sam68, the Src-associated substrate during mitosis of 68 kDa, belongs to the large class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) domain family of RNA-binding proteins...
  26. Ishizuka A, Hasegawa Y, Ishida K, Yanaka K, Nakagawa S. Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1. Genes Cells. 2014;19:704-21 pubmed publisher
    ..These observations suggest that Gomafu indirectly modulates the function of the splicing factors SF1 and Celf3 by sequestering these proteins into separate nuclear bodies. ..
  27. Duran A, Linares J, Galvez A, Wikenheiser K, Flores J, Diaz Meco M, et al. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell. 2008;13:343-54 pubmed publisher
    ..Here, we show that the signaling adaptor p62 is induced by Ras, its levels are increased in human tumors, and it is required for Ras-induced survival and ..
  28. Agger R, Freimuth P. Purification and cDNA sequence of a murine protein homologous to the human p62 tyrosine phosphoprotein that associates with the Ras GTPase-activating protein p120 GAP. Gene. 1995;158:307-8 pubmed
    ..Corresponding cDNA clones code for a protein that is closely related to a 62-kDa human protein (p62) that associates with the Ras GTPase-activating protein, p120 GAP, suggesting that p62 may have a dendritic cell-..
  29. Lawrence P, Schafer E, Rieder E. The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells. Virology. 2012;425:40-52 pubmed publisher
    ..Here, we demonstrated that the FMDV 3C(pro) induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS)...
  30. Feracci M, Foot J, Grellscheid S, Danilenko M, Stehle R, Gonchar O, et al. Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nat Commun. 2016;7:10355 pubmed publisher
    b>Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins...
  31. Moritz S, Lehmann S, Faissner A, von Holst A. An induction gene trap screen in neural stem cells reveals an instructive function of the niche and identifies the splicing regulator sam68 as a tenascin-C-regulated target gene. Stem Cells. 2008;26:2321-31 pubmed publisher
    ..Our pilot screen identified Sam68 as a target of Tnc signaling in NSCs...
  32. Anderton R, Price L, Turner B, Meloni B, Mitrpant C, Mastaglia F, et al. Co-regulation of survival of motor neuron and Bcl-xL expression: implications for neuroprotection in spinal muscular atrophy. Neuroscience. 2012;220:228-36 pubmed publisher
    ..Interestingly, the anti-apoptotic Bcl-x isoform, Bcl-xL, is reduced in SMA. In a related finding, Sam68, an RNA-binding protein, was found to modulate splicing of SMN and Bcl-xL transcripts, promoting SMN?7 and pro-..
  33. Song J, Richard S. Sam68 Regulates S6K1 Alternative Splicing during Adipogenesis. Mol Cell Biol. 2015;35:1926-39 pubmed publisher
    The requirement for alternative splicing during adipogenesis is poorly understood. The Sam68 RNA binding protein is a known regulator of alternative splicing, and mice deficient for Sam68 exhibit adipogenesis defects due to defective ..
  34. Huot M, Vogel G, Zabarauskas A, Ngo C, Coulombe Huntington J, Majewski J, et al. The Sam68 STAR RNA-binding protein regulates mTOR alternative splicing during adipogenesis. Mol Cell. 2012;46:187-99 pubmed publisher
    We report that mice ablated for the Sam68 RNA-binding protein exhibit a lean phenotype as a result of increased energy expenditure, decreased commitment to early adipocyte progenitors, and defects in adipogenic differentiation...
  35. Paronetto M, Bianchi E, Geremia R, Sette C. Dynamic expression of the RNA-binding protein Sam68 during mouse pre-implantation development. Gene Expr Patterns. 2008;8:311-22 pubmed publisher
    The STAR protein Sam68 (KHDRBS1) is involved in several aspects of post-transcriptional mRNA metabolism. Herein, we have investigated the expression and subcellular localization of Sam68 during early mouse embryogenesis...
  36. Klein M, Castillo P, Jordan B. Coordination between Translation and Degradation Regulates Inducibility of mGluR-LTD. Cell Rep. 2015;: pubmed publisher
    ..Moreover, proteasome inhibition can rescue mGluR-LTD in mice null for the RNA binding protein Sam68, which we show here lack mGluR-dependent translation and LTD...
  37. Sun X, Fu K, Hodgson A, Wier E, Wen M, Kamenyeva O, et al. Sam68 Is Required for DNA Damage Responses via Regulating Poly(ADP-ribosyl)ation. PLoS Biol. 2016;14:e1002543 pubmed publisher
    ..Here, we identified Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel signaling molecule in DNA damage responses (DDRs)...
  38. Versteeg H, Hoedemaeker I, Diks S, Stam J, Spaargaren M, van Bergen en Henegouwen P, et al. Factor VIIa/tissue factor-induced signaling via activation of Src-like kinases, phosphatidylinositol 3-kinase, and Rac. J Biol Chem. 2000;275:28750-6 pubmed
    ..We propose that this Src family member/PI3K/Rac-dependent signaling pathway is a major mediator of factor VIIa/TF effects in pathophysiology. ..
  39. Chandrasekar B, Mummidi S, Valente A, Patel D, Bailey S, Freeman G, et al. The pro-atherogenic cytokine interleukin-18 induces CXCL16 expression in rat aortic smooth muscle cells via MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, c-Src, phosphatidylinositol 3-kinase, Akt. J Biol Chem. 2005;280:26263-77 pubmed
    ..These data provide for the first time a mechanism of IL-18-mediated CXCL16 gene transcription and CXCL16-dependent ASMC proliferation and suggest a role for IL-18-CXCL16 cross-talk in atherogenesis and restenosis following angioplasty. ..
  40. Cote J, Boisvert F, Boulanger M, Bedford M, Richard S. Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1. Mol Biol Cell. 2003;14:274-87 pubmed
    ..Herein, we report that Sam68, a heteronuclear ribonucleoprotein K homology domain containing RNA binding protein, associates with and is ..
  41. Li N, Ngo C, Aleynikova O, Beauchemin N, Richard S. The p53 status can influence the role of Sam68 in tumorigenesis. Oncotarget. 2016;7:71651-71659 pubmed publisher
    ..Here we show, using two classical mouse cancer models, that the role of KH-type RNA binding protein, Sam68, in tumor development can be influenced by the status of the p53 tumor suppressor...
  42. Lazer G, Pe er L, Schapira V, Richard S, Katzav S. The association of Sam68 with Vav1 contributes to tumorigenesis. Cell Signal. 2007;19:2479-86 pubmed
    ..Using a proteomics approach, we identified Sam68 as a Vav1SH3C-associating protein...
  43. Taylor S, Anafi M, Pawson T, Shalloway D. Functional interaction between c-Src and its mitotic target, Sam 68. J Biol Chem. 1995;270:10120-4 pubmed
    ..The results suggest that the selection of Sam 68 as a mitotic target by c-Src is the result of highly specific interaction with SH2 and SH3 domains and that this interaction may modulate the RNA binding activity of Sam 68...
  44. Maroni P, Citterio L, Piccoletti R, Bendinelli P. Sam68 and ERKs regulate leptin-induced expression of OB-Rb mRNA in C2C12 myotubes. Mol Cell Endocrinol. 2009;309:26-31 pubmed publisher
    ..The Sam68 STAR protein has been implicated in leptin signal transduction as an adaptor molecule useful to recruit other ..
  45. Fu K, Sun X, Wier E, Hodgson A, Hobbs R, Wan F. Sam68/KHDRBS1-dependent NF-?B activation confers radioprotection to the colon epithelium in ?-irradiated mice. elife. 2016;5: pubmed publisher
    Previously we reported that Src-associated-substrate-during-mitosis-of-68kDa (Sam68/KHDRBS1) is pivotal for DNA damage-stimulated NF-?B transactivation of anti-apoptotic genes (Fu et al., 2016)...
  46. Pagliarini V, Pelosi L, Bustamante M, Nobili A, Berardinelli M, D Amelio M, et al. SAM68 is a physiological regulator of SMN2 splicing in spinal muscular atrophy. J Cell Biol. 2015;211:77-90 pubmed publisher
    ..We found that knockout of the splicing factor SAM68 partially rescued body weight and viability of SMAΔ7 mice...
  47. Messina V, Meikar O, Paronetto M, Calabretta S, Geremia R, Kotaja N, et al. The RNA binding protein SAM68 transiently localizes in the chromatoid body of male germ cells and influences expression of select microRNAs. PLoS ONE. 2012;7:e39729 pubmed publisher
    ..Herein, we show that the RNA binding protein SAM68 transiently localizes in the CB, in concomitance with the meiotic divisions of mouse spermatocytes...
  48. Pedrotti S, Busà R, Compagnucci C, Sette C. The RNA recognition motif protein RBM11 is a novel tissue-specific splicing regulator. Nucleic Acids Res. 2012;40:1021-32 pubmed publisher
    ..Thus, our findings identify RBM11 as a novel tissue-specific splicing factor with potential implication in the regulation of alternative splicing during neuron and germ cell differentiation. ..
  49. Qian J, Zhao W, Miao X, Li L, Zhang D. Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-?B activation in ulcerative colitis. Mol Immunol. 2016;75:48-59 pubmed publisher
    Sam68 (Src-associated substrate during mitosis of 68 KDa), also known as KHDRBS1 (KH domain containing, RNA binding, signal transduction associated 1), belongs to the prototypic member of the signal transduction activator of RNA (STAR) ..