The ser/threonine protein kinase encoded by the mos proto-oncogene plays a key cell cycle regulatory role during meiosis. Mos protein is necessary for the activation and stabilization of the M-phase promoter MPF. As part of a large multiprotein complex known as cytostatic factor (CSF), Mos causes vertebrate eggs to stagnate in mid-phase II. Mos expression in somatic cells can cause cell cycle disturbances, leading to cytotoxicity and tumor transformation. All known biological activities of Mos are mediated by activation of the mitogen-activated protein (MAP) kinase pathway.
The first oncogene found to belong to the serine/threonine protein kinase superfamily was c-mos. The mos gene was found to be a cellular homolog of the retroviral oncogene. As part of the Moloney Murine Sarcoma Virus, the mos gene encodes a 374 amino acid long protein. The thirtieth amino acid present at the amino terminus of vMos is produced by fusion between the viral env sequence (5 amino acids) and the sequence upstream of the c-mas start codon (26 amino acids). The protein kinase domain ranges from v-Mos amino acid residues 100 to the carboxy terminus.
The most satisfactory model for M-phase (mitosis and meiosis) regulation involves the mutual regulation of key protein kinases. For mitosis, these protein kinases include MPF, NIMA, MPM2 kinase, and MAP kinase (or their homologs). In addition to these kinases, Mos is also required to regulate spinal meiosis. The role of Mos in regulating MPF and MAP kinases has been extensively investigated. Based on these studies, the mechanisms of mutual regulation or feedback regulation of these kinases have begun to emerge.
To understand the biochemical function of Mos in cells, attempts have been made to identify Mosassociated proteins. Initially, gel fractionation studies showed that Mos can be divided into large and large molecular complexes in Mos-transformed cells. Of course, Mos is part of the large multiprotein complex CSF in eggs. So far, Mos has been linked to microtubules and intermediate silk proteins vimentin. The Moss tubulin complex also contains f34cdc2. It has also been shown that another p34cdc2 isoform called p35cd is associated with v-Mos in transformed cells. The correlation between Mos and microtubules provides support for the role of Mos in regulating the structure and function of the meiotic spindle. However, the nature of Mos microtubule interactions is complex. Under conditions where the microtubules dissociate to produce large, medium, and small sizes, Mos is preferentially positioned in the largest microtubule portion (68). Therefore, as expected from its very specific role, the interaction of Mos with microtubules is likely to be affected by microtubule-associated proteins (MAPs). The question that remains to be resolved is whether Mos binds to microtubules and only phosphorylates MAPKK or any other protein. As mentioned above, Mos can phosphorylate tubulin in vitro, but whether it is phosphorylated in vivo remains to be seen.
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