Phosphorylation of WDR77 (MEP50) on threonine-5 by cyclin-dependent kinase 4 (CDK4), as part of the complex cyclin D1: CDK4:PRMT5:WDR77 enhances PRMT5:WDR77 methyltransferase activity, which triggers events associated with cyclin D1-dependent neoplastic growth (Aggarwal et al. 2011). Cyclin D1 is an allosteric regulator of CDK4 and CDK6, mediating growth factor-dependent G1-phase progression. Growth factor stimulation induces cyclin D1 expression, its association with CDK4 and nuclear accumulation during mid-G1. Active cyclin D1:CDK4 catalyzes the phosphorylation-dependent inactivation of retinoblastoma (RB) family proteins (Diehl 2002, Gladden & Diehl 2005). Following the G1/S transition, cyclin D1 accumulation is opposed by phosphorylation of threonine-286 (T286) by glycogen synthase kinase 3 beta (GSK3beta), which promotes cyclin D1 nuclear export (Alt et al. 2000).
Kim, JK, Nakagawa, H, Aggarwal, P, Herlyn, M, Vaites, LP, Hua, X, McMahon, SB, Gurung, B, Rustgi, AK, Mellert, H, Diehl, JA
cyclin-dependent protein serine/threonine kinase regulator activity of CCND1:CDK4:PRMT5:WDR77 [nucleoplasm]
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