proto oncogene proteins c mos


Summary: Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.

Top Publications

  1. Nagao Y. Definitive expression of c-mos in late meiotic prophase leads to phosphorylation of a 34 kda protein in cultured rat spermatocytes. Cell Biol Int. 2002;26:193-201 pubmed
    ..4-4.5, and cdc2 was not detected, making it different from cdc2 (p34). These results suggest that the phosphorylation of the 34 kDa protein by the c-mos signal may play a crucial role in the meiotic division of rat spermatocytes. ..
  2. Rosenberg M, Aversa C, Wallace R, Propst F. Expression of the v-Mos oncogene in male meiotic germ cells of transgenic mice results in metaphase arrest. Cell Growth Differ. 1995;6:325-36 pubmed
    ..Thus, overexpression of pp39v-mos during male germ cell meiosis resulted in an alteration of various cell cycle related kinases and cytostatic factor-like arrest at MI. ..
  3. Tunquist B, Schwab M, Chen L, Maller J. The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Curr Biol. 2002;12:1027-33 pubmed
    ..Both pathways are independent of each other, but each appears to block activation of the APC, which is required for cyclin B degradation and the metaphase/anaphase transition. ..
  4. Hashimoto N, Watanabe N, Furuta Y, Tamemoto H, Sagata N, Yokoyama M, et al. Parthenogenetic activation of oocytes in c-mos-deficient mice. Nature. 1994;370:68-71 pubmed
    ..The results indicate that in mice Mos plays a role in the second meiotic metaphase arrest, but does not seem to be essential for the initiation of oocyte maturation, spermatogenesis or somatic cell cycle. ..
  5. Inoue D, Ohe M, Kanemori Y, Nobui T, Sagata N. A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs. Nature. 2007;446:1100-4 pubmed
    ..These results clarify the direct link of the classical Mos-MAPK pathway to Erp1 in meiotic arrest of vertebrate oocytes. ..
  6. Ueno S, Sagata N. Requirement for both EDEN and AUUUA motifs in translational arrest of Mos mRNA upon fertilization of Xenopus eggs. Dev Biol. 2002;250:156-67 pubmed
    ..These results suggest that the EDEN, only together with appropriately positioned AUUUA motifs and a trans-acting factor(s), can efficiently deadenylate and hence translationally arrest Mos (as well as Eg2) mRNA after fertilization. ..
  7. Bhatt R, Ferrell J. The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. Science. 1999;286:1362-5 pubmed
    ..Replenishing Rsk-depleted extracts with catalytically competent Rsk protein restored the ability of the extracts to undergo mitotic arrest. Rsk appears to be essential for cytostatic factor arrest. ..
  8. Tsurumi C, Hoffmann S, Geley S, Graeser R, Polanski Z. The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes. J Cell Biol. 2004;167:1037-50 pubmed
    ..Thus, SAC proteins are required for checkpoint functions in meiosis I and II, but, in contrast to frog eggs, the SAC is not required for establishing or maintaining the CSF arrest in mouse oocytes. ..
  9. Sagata N, Oskarsson M, Copeland T, Brumbaugh J, Vande Woude G. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature. 1988;335:519-25 pubmed
    ..Microinjection of mos-specific antisense oligonucleotides into oocytes not only prevents expression of pp39mos, but also blocks germinal vesicle breakdown, indicating that it functions during reinitiation of meiotic division. ..

More Information


  1. Reimann J, Jackson P. Emi1 is required for cytostatic factor arrest in vertebrate eggs. Nature. 2002;416:850-4 pubmed
    ..Addition of Emi1 to these Emi1-depleted extracts blocks premature inactivation of the CSF-arrested state. Emi1 is required to arrest unfertilized eggs at metaphase of meiosis II and seems to be the long-sought mediator of CSF activity. ..
  2. Nebreda A, Ferby I. Regulation of the meiotic cell cycle in oocytes. Curr Opin Cell Biol. 2000;12:666-75 pubmed
    ..New insights have been made recently into the signalling mechanisms that induce G2-arrested oocytes to resume and complete the meiotic cell cycle. ..
  3. Kim M, Yuan X, Okumura S, Ishikawa F. Successful inactivation of endogenous Oct-3/4 and c-mos genes in mouse preimplantation embryos and oocytes using short interfering RNAs. Biochem Biophys Res Commun. 2002;296:1372-7 pubmed
    ..Accordingly, we concluded that siRNA is a useful tool in molecular studies on the early development of mouse. ..
  4. Tunquist B, Maller J. Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev. 2003;17:683-710 pubmed
  5. Ferrara D, Palmiero C, Branno M, Pierantoni R, Minucci S. Testicular activity of Mos in the frog, Rana esculenta: a new role in spermatogonial proliferation. Biol Reprod. 2004;70:1782-9 pubmed
    ..These results strongly indicate that the c-mos proto-oncogene exerts a new role associated to the regulation of spermatogonial proliferation...
  6. Puls A, Proikas Cezanne T, Marquardt B, Propst F, Stabel S. Kinase activities of c-Mos and v-Mos proteins: a single amino acid exchange is responsible for constitutive activation of the 124 v-Mos kinase. Oncogene. 1995;10:623-30 pubmed
    ..We hypothesize that the Arg145-->Gly mutation found in 124 v-Mos mimicks a conformational change which might be an obligatory step in the activation of c-Mos in vivo. ..
  7. Verlhac M, Kubiak J, Weber M, Geraud G, Colledge W, Evans M, et al. Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse. Development. 1996;122:815-22 pubmed
    ..These observations present the first evidence, in intact oocytes, of a role for the Mos/.../MAP kinase cascade in the control of microtubule and chromatin organization during meiosis. ..
  8. Colledge W, Carlton M, Udy G, Evans M. Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs. Nature. 1994;370:65-8 pubmed
    ..Mutant females also develop ovarian cysts. These results demonstrate that a major role for pp39mos is to prevent the spontaneous parthenogenetic activation of unfertilized eggs. ..
  9. Paronetto M, Giorda E, Carsetti R, Rossi P, Geremia R, Sette C. Functional interaction between p90Rsk2 and Emi1 contributes to the metaphase arrest of mouse oocytes. EMBO J. 2004;23:4649-59 pubmed
  10. Sagata N. What does Mos do in oocytes and somatic cells?. Bioessays. 1997;19:13-21 pubmed
    ..This review discusses the cellular basis that may enable Mos to act differently in oocytes and somatic cells. ..
  11. Liu H, Vuyyuru V, Pham C, Yang Y, Singh B. Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association. Oncogene. 1999;18:3461-70 pubmed
  12. Sasaki K, Chiba K. Fertilization blocks apoptosis of starfish eggs by inactivation of the MAP kinase pathway. Dev Biol. 2001;237:18-28 pubmed
    ..Fertilization inactivates the MAP kinase pathway and suppresses apoptosis, followed by normal development. ..
  13. Tunquist B, Eyers P, Chen L, Lewellyn A, Maller J. Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. J Cell Biol. 2003;163:1231-42 pubmed
    ..These results suggest a model in which CSF arrest by Mos is mediated by the Mad1 and Mad2 proteins in a manner distinct from the spindle checkpoint. ..
  14. Newman B, Dai Y. Transcription of c-mos protooncogene in the pig involves both tissue-specific promoters and alternative polyadenylation sites. Mol Reprod Dev. 1996;44:275-88 pubmed
    ..The significance of these transcripts in terms of translational control is discussed. ..
  15. Nishiyama T, Ohsumi K, Kishimoto T. Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature. 2007;446:1096-9 pubmed
    ..Thus, Mos and Erp1 collaboratively establish and maintain metaphase II arrest in Xenopus eggs. The link between Mos and Erp1 provides a molecular explanation for the integral mechanism of CSF arrest in unfertilized vertebrate eggs. ..
  16. Verlhac M, Lefebvre C, Kubiak J, Umbhauer M, Rassinier P, Colledge W, et al. Mos activates MAP kinase in mouse oocytes through two opposite pathways. EMBO J. 2000;19:6065-74 pubmed
    ..We also show that a phosphatase activity inactivates MAPK, and that Mos can overcome this inhibitory activity. Thus Mos activates MAPK through two opposite pathways: activation of MEK1 and inhibition of a phosphatase. ..
  17. Dupré A, Jessus C, Ozon R, Haccard O. Mos is not required for the initiation of meiotic maturation in Xenopus oocytes. EMBO J. 2002;21:4026-36 pubmed
    ..We propose that the unique and conserved role of Mos is to prevent mitotic cell cycles of the female gamete until the fertilization in Xenopus, starfish and mouse oocytes. ..
  18. Oh B, Hampl A, Eppig J, Solter D, Knowles B. SPIN, a substrate in the MAP kinase pathway in mouse oocytes. Mol Reprod Dev. 1998;50:240-9 pubmed
    ..These findings suggest that SPIN is a substrate in the MOS/ MAP kinase pathway and further that this phosphorylation of SPIN may be essential for its interaction with the spindle. ..
  19. Yamano H, Gannon J, Hunt T. The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe. EMBO J. 1996;15:5268-79 pubmed
  20. Lazar S, Galiani D, Dekel N. cAMP-Dependent PKA negatively regulates polyadenylation of c-mos mRNA in rat oocytes. Mol Endocrinol. 2002;16:331-41 pubmed
    ..We also demonstrate that stimulation of Mos synthesis in the rat does not require an active MAPK. ..
  21. Yue J, Ferrell J. Mechanistic studies of the mitotic activation of Mos. Mol Cell Biol. 2006;26:5300-9 pubmed
    ..Our work suggests that Ser 105 dephosphorylation represents a novel mechanism for reorienting helix alphaC. ..
  22. Voelker G, Spellman G. Nuclear and mitochondrial DNA evidence of polyphyly in the avian superfamily Muscicapoidea. Mol Phylogenet Evol. 2004;30:386-94 pubmed
    ..Our analyses suggest that c-mos was only marginally useful in resolving these "deep" phylogenetic relationships. ..
  23. Lazar S, Gershon E, Dekel N. Selective degradation of cyclin B1 mRNA in rat oocytes by RNA interference (RNAi). J Mol Endocrinol. 2004;33:73-85 pubmed
    ..We conclude that an active MPF in rat oocytes is necessary for c-mos mRNA polyadenylation and Mos translation. ..
  24. Hashiba Y, Asada Y, Heikinheimo O, Lanzendorf S, Mizutani S. Microinjection of antisense c-mos oligonucleotides prevents the progression of meiosis in human and hamster oocytes. Fertil Steril. 2001;76:143-7 pubmed
    ..0001) and human (P=.05) oocytes. Thus, c-mos proto-oncogene may be one of the critical regulators of meiosis in these two species. ..
  25. Murakami M, Vande Woude G. Analysis of the early embryonic cell cycles of Xenopus; regulation of cell cycle length by Xe-wee1 and Mos. Development. 1998;125:237-48 pubmed
    ..Our experiments indicate that Mos/MAPK can also contribute to cell cycle length. ..
  26. Sorrentino V, McKinney M, Giorgi M, Geremia R, Fleissner E. Expression of cellular protooncogenes in the mouse male germ line: a distinctive 2.4-kilobase pim-1 transcript is expressed in haploid postmeiotic cells. Proc Natl Acad Sci U S A. 1988;85:2191-5 pubmed
    ..In particular, analysis of expression of the three members of the ras gene family indicates a distinct temporal differential regulation in the expression of the Harvey, Kirsten, and N-ras genes in these germ cells...
  27. Van Sloun P, Jansen J, Weeda G, Mullenders L, van Zeeland A, Lohman P, et al. The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage. Nucleic Acids Res. 1999;27:3276-82 pubmed
    ..Possibly, to avoid the accumulation of mutated cells, ES cells rely on the induction of a strong apoptotic response with a simultaneous shutting down of NER activity. ..
  28. Grabarek J, Plusa B, Glover D, Zernicka Goetz M. Efficient delivery of dsRNA into zona-enclosed mouse oocytes and preimplantation embryos by electroporation. Genesis. 2002;32:269-76 pubmed
    ..These effects could be observed in multiple oocytes or embryos allowed to develop together following electroporation. ..
  29. Wu Q, Guo Y, Yamada A, Perry J, Wang M, Araki M, et al. A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest. Curr Biol. 2007;17:213-24 pubmed
    ..This balance allows proper maintenance of Cyclin B levels and Cdc2 kinase activity during CSF arrest. ..
  30. Lenormand J, Benayoun B, Guillier M, Vandromme M, Leibovitch M, Leibovitch S. Mos activates myogenic differentiation by promoting heterodimerization of MyoD and E12 proteins. Mol Cell Biol. 1997;17:584-93 pubmed
    ..These data support a novel function for Mos as a mediator (coregulator) of muscle-specific gene(s) expression. ..
  31. Lieberman S, Ruderman J. CK2 beta, which inhibits Mos function, binds to a discrete domain in the N-terminus of Mos. Dev Biol. 2004;268:271-9 pubmed
    ..These results argue that CK2 beta directly binds and inhibits Mos rather than a downstream component, and support that CK2 beta functions as a molecular buffer that prevents premature MAPK activation and oocyte maturation. ..
  32. Hennebold J, Tanaka M, Saito J, Hanson B, Adashi E. Ovary-selective genes I: the generation and characterization of an ovary-selective complementary deoxyribonucleic acid library. Endocrinology. 2000;141:2725-34 pubmed
    ..These ovary-selective genes may have significant implications for the understanding of ovarian function in molecular terms and for the development of innovative strategies for the promotion of fertility or its control. ..
  33. Athanasiou A, Perunovic B, Quilty R, Gorgoulis V, Kittas C, Love S. Expression of mos in ependymal gliomas. Am J Clin Pathol. 2003;120:699-705 pubmed
    ..05) but not with overall survival. Our results suggest that overexpression of mos identifies a biologically aggressive subgroup of ependymal tumors and may be involved in their neoplastic progression. ..
  34. Kanduri C, Raman R. Tissue-specific characterisation of DNA methylation in the gonad-specific proto-oncogene, c-mos, in the male laboratory mouse. Int J Dev Biol. 1999;43:91-4 pubmed
    ..In contrast to these tissues, in the mouse fibroblast cell line L929, all the analysed sites were completely methylated. ..
  35. Motola S, Cao X, Popliker M, Tsafriri A. Involvement of mitogen-activated protein kinase (MAPK) pathway in LH- and meiosis-activating sterol (MAS)-induced maturation in rat and mouse oocytes. Mol Reprod Dev. 2008;75:1533-41 pubmed publisher
    ..MAPK/MOS activation, whether in the somatic compartment or in denuded oocytes, is required for MAS- like LH-, FSH-, or EGF-induced resumption of meiosis. ..
  36. Paillard L, Omilli F, Legagneux V, Bassez T, Maniey D, Osborne H. EDEN and EDEN-BP, a cis element and an associated factor that mediate sequence-specific mRNA deadenylation in Xenopus embryos. EMBO J. 1998;17:278-87 pubmed
    ..Therefore, EDEN-BP constitutes the first trans-acting factor for which an essential role in the specificity of mRNA deadenylation has been directly demonstrated. ..
  37. Angeli D, Ferrell J, Sontag E. Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc Natl Acad Sci U S A. 2004;101:1822-7 pubmed
  38. Yoshida N, Mita K, Yamashita M. Function of the Mos/MAPK pathway during oocyte maturation in the Japanese brown frog Rana japonica. Mol Reprod Dev. 2000;57:88-98 pubmed
  39. Gorgoulis V, Zacharatos P, Mariatos G, Liloglou T, Kokotas S, Kastrinakis N, et al. Deregulated expression of c-mos in non-small cell lung carcinomas: relationship with p53 status, genomic instability, and tumor kinetics. Cancer Res. 2001;61:538-49 pubmed
    ..This finding also strengthens the concept that wild-type p53 plays a "safeguard" role in preventing oncogene-mediated activation. ..
  40. Pham C, Vuyyuru V, Yang Y, Bai W, Singh B. Evidence for an important role of serine 16 and its phosphorylation in the stabilization of c-Mos. Oncogene. 1999;18:4287-94 pubmed
    ..Thus, our results indicate that Ser-16 has an important role in the regulation of c-Mos and that phosphorylation at Ser-16 may inhibit proteolysis of c-Mos. ..
  41. Reverte C, Yuan L, Keady B, Lacza C, Attfield K, Mahon G, et al. XGef is a CPEB-interacting protein involved in Xenopus oocyte maturation. Dev Biol. 2003;255:383-98 pubmed
    ..These results suggest that XGef may be an early acting component of the progesterone-induced oocyte maturation pathway. ..
  42. Lovette I, Bermingham E. c-mos variation in songbirds: molecular evolution, phylogenetic implications, and comparisons with mitochondrial differentiation. Mol Biol Evol. 2000;17:1569-77 pubmed
  43. Hirao Y, Eppig J. Parthenogenetic development of Mos-deficient mouse oocytes. Mol Reprod Dev. 1997;48:391-6 pubmed
    ..Aberrant meiotic divisions commonly observed in Mos-/- oocytes in vitro may adversely affect preimplantation development and reduce the frequency of blastocyst formation even under the best culture conditions. ..
  44. Haccard O, Jessus C. Redundant pathways for Cdc2 activation in Xenopus oocyte: either cyclin B or Mos synthesis. EMBO Rep. 2006;7:321-5 pubmed
    ..We conclude that the specific synthesis of either B-type cyclins or c-Mos, induced by progesterone, is required to induce meiotic maturation. The two pathways seem to be functionally redundant. ..
  45. Maller J, Schwab M, Gross S, Taieb F, Roberts B, Tunquist B. The mechanism of CSF arrest in vertebrate oocytes. Mol Cell Endocrinol. 2002;187:173-8 pubmed
    ..CSF arrest in vertebrate oocytes by p90(Rsk) provides a link between the MAPK pathway and the spindle assembly checkpoint in the cell cycle. ..
  46. Marangos P, Carroll J. Fertilization and InsP3-induced Ca2+ release stimulate a persistent increase in the rate of degradation of cyclin B1 specifically in mature mouse oocytes. Dev Biol. 2004;272:26-38 pubmed
    ..Furthermore, this Ca2+ -induced increase in degradation of cyclin B1 requires factors specific to mature oocytes, and that to overcome arrest at MII, Ca2+ acts to release the CSF-mediated brake on cyclin B1 destruction. ..
  47. Kishimoto T. Developmental biology: cell cycle unleashed. Nature. 2005;437:963-5 pubmed
  48. Carazo Salas R, Gruss O, Mattaj I, Karsenti E. Ran-GTP coordinates regulation of microtubule nucleation and dynamics during mitotic-spindle assembly. Nat Cell Biol. 2001;3:228-34 pubmed
    ..We also show that inhibition of Ran-GTP production, even in the presence of duplicated centrosomes and kinetochores, prevents assembly of a bipolar spindle in M-phase extracts. ..
  49. Charlesworth A, Ridge J, King L, MacNicol M, MacNicol A. A novel regulatory element determines the timing of Mos mRNA translation during Xenopus oocyte maturation. EMBO J. 2002;21:2798-806 pubmed
    ..Our findings suggest that the timing of maternal mRNA translation is controlled through signal transduction pathways targeting distinct 3' UTR mRNA elements. ..
  50. Tung J, Padmanabhan K, Hansen D, Richter J, Jackson P. Translational unmasking of Emi2 directs cytostatic factor arrest in meiosis II. Cell Cycle. 2007;6:725-31 pubmed
    ..Our results demonstrate that cytoplasmic polyadenylation and translational unmasking of Emi2 directs meiosis II-specific CSF arrest. ..
  51. Kundra V, Soker S, Zetter B. Excess early signaling activity inhibits cellular chemotaxis toward PDGF-BB. Oncogene. 1994;9:1429-35 pubmed
    ..In addition, our results show that the signals that mediate chemotaxis are separable from those that regulate unstimulated random motility in the same cells. ..
  52. Wang X, Yew N, Peloquin J, Vande Woude G, Borisy G. Mos oncogene product associates with kinetochores in mammalian somatic cells and disrupts mitotic progression. Proc Natl Acad Sci U S A. 1994;91:8329-33 pubmed
    ..Our results suggest that mitotic blockage by Mos may result from an action of the Mos kinase on the kinetochores, thus increasing chromosome instability and preventing normal congression. ..
  53. Amiel A, Leclère L, Robert L, Chevalier S, Houliston E. Conserved functions for Mos in eumetazoan oocyte maturation revealed by studies in a cnidarian. Curr Biol. 2009;19:305-11 pubmed publisher
    ..Our findings indicate that Mos appeared early during animal evolution as an oocyte-expressed kinase and functioned ancestrally in regulating core specializations of female meiosis. ..