M-phase phosphoprotein 9 (MPHOSPH9)

M-phase phosphoprotein 9 (MPHOSPH9) is a cell cycle-regulated, centrosome-associated adaptor protein that negatively regulates the assembly of primary cilia by recruiting and maintaining the CP110-CEP97 complex at the mother centriole. During ciliogenesis, MPHOSPH9 undergoes phosphorylation-mediated degradation via the ubiquitin-proteasome system initiated by Tau tubulin kinase 2 (TTBK2), allowing removal of CP110 and CEP97, which facilitates cilia formation. Upregulation of MPHOSPH9 is associated with poor prognosis in gastric cancer, partly through activation of mTOR signaling and increased cell proliferation; it is also implicated in multiple sclerosis and spinocerebellar ataxia 11. MPHOSPH9 is thus emerging as a disease-relevant node in cell cycle and cilium signaling, with potential as both a biomarker and therapeutic target.

Other names

MPP9MPP-9M-phase phosphoprotein 9MPHOSPH9

For mTOR pathway inhibition: MPHOSPH9 upregulation reduces the inhibitory effects of mTOR inhibitors on cell survival in gastric cancer cells, suggesting that targeting MPHOSPH9 could sensitize tumors to mTOR-targeted therapies. Targeting MPHOSPH9 may affect ciliogenesis regulation by disturbing CP110-CEP97 complex assembly/disassembly at the centriole.