Meta-Biol

• Pathways

CDKN1B (also known as p27 KIP) is an inhibitor of G1 cyclin dependent kinase complexes. CDKN1B interacts with CCND1:CDK4/6 complexes to prevent progression into S phase (reviewed in Vermeulen et al, 2003; Hnit et al, 2015). Relief of CDKN1B-mediated inhibition in response to mitogenic signals is accomplished by multiple mechanisms including localization, transcriptional, translational and proteolytic regulation of CDKN1B.
CDKN1B is phosphorylated at serine 10 during G1 in response to serum and estrogen stimulation, resulting in its XPO1-dependent nuclear export (Ishida et al, 2000; Rodier et al, 2001; Ishida et al, 2003). RAS signaling and PRKCZ-dependent MAPK1 nuclear translocation is required for nuclear export of CDKN1B in response to estrogen stimulation in MCF cells (Aktas et al, 1997; Cheng et al, 1998; Foster et al, 2003; Castoria et al, 2004; Kawada et al, 1997; Migliaccio et al, 1996). Although MAP kinases have been shown to phosphorylate CDKN1B in vitro, it has not been demonstrated in vivo. In another study, UHMK1 was identified as the kinase responsible for S10 phosphorylation in response to serum stimulation (Boehm et al, 2001).