Alternative titles; symbols
HGNC Approved Gene Symbol: MPHOSPH6
Cytogenetic location: 16q23.3 Genomic coordinates (GRCh38): 16:82,148,162-82,170,224 (from NCBI)
Progression of cells from interphase to mitosis involves alterations in cell structures and activities. The transition from G2 to M phase is induced by M phase-promoting factor, or MPF (see CCNB1; 123836). In M phase, many proteins are phosphorylated directly by MPF or indirectly by kinases activated by MPF. These M-phase phosphoproteins (MPPs, or MPHOSPHs) permit disassembly of interphase structures and generation of M-phase enzymatic activities and structures.
By treating bacterial expression libraries with M-phase cytosol containing the relevant kinases in the presence of a phosphatase inhibitor, followed by immunoscreening with MPM2 antibody, Matsumoto-Taniura et al. (1996) isolated cDNAs for a number of MPHOSPHs, including MPHOSPH6, which they called MPP6. Immunoblot analysis showed that when phosphorylated, MPHOSPH6 is expressed as a 17-kD protein in M-phase cells. Immunofluorescence microscopy localized MPHOSPH6 throughout the nucleus, with a modest concentration in nucleoli, in interphase, and throughout the cell in mitotic cells.
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3-prime untranslated regions. In yeast, 3-prime-to-5-prime mRNA degradation is mediated by the exosome, a multisubunit particle. Chen et al. (2001) purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. They identified the following protein subunits within the human exosome: p7, which is homologous to the yeast Rrp4 protein (602238); p8, which is homologous to the yeast Rrp42 protein (606488); p9, which is homologous to the yeast Rrp43 protein (OIP2; 606019); p10, which is homologous to the yeast Rrp40 protein (606489); p11, which is homologous to the yeast Mtr3 protein (606490); p12A, which is homologous to the yeast Rrp41 protein (606491); p12B, which is homologous to the yeast Rrp46 protein (606492); and p13, which is homologous to the yeast Csl4 protein (606493). They also identified 2 exosome-associated factors, p1 (600478) and p14 (MPP6), that were not homologous to any yeast exosome components.
Using a cell-free RNA decay system, Chen et al. (2001) demonstrated that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. They found that the mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition required certain ARE-binding proteins that could interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.
The International Radiation Hybrid Mapping Consortium mapped the MPHOSPH6 gene to chromosome 16 (AA041294).
Chen, C.-Y., Gherzi, R., Ong, S.-E., Chan, E. L., Raijmakers, R., Pruijn, G. J. M., Stoecklin, G., Moroni, C., Mann, M., Karin, M. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107: 451-464, 2001. [PubMed: 11719186] [Full Text: https://doi.org/10.1016/s0092-8674(01)00578-5]
Matsumoto-Taniura, N., Pirollet, F., Monroe, R., Gerace, L., Westendorf, J. M. Identification of novel M phase phosphoproteins by expression cloning. Molec. Biol. Cell 7: 1455-1469, 1996. [PubMed: 8885239] [Full Text: https://doi.org/10.1091/mbc.7.9.1455]