Reactome | CDKN1B is phosphorylated in response to estrogen

CDKN1B is phosphorylated in response to estrogen

Stable Identifier

R-HSA-9632868

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

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CDKN1B is phosphorylated in response to estrogen

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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).

Literature References

PubMed ID	Title	Journal	Year
26279144	p27(Kip1) signaling: Transcriptional and post-translational regulation Hnit, SS, Xie, C, Yao, M, Holst, J, Bensoussan, A, De Souza, P, Li, Z, Dong, Q	Int. J. Biochem. Cell Biol.	2015
9199319	Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1 Aktas, H, Cai, H, Cooper, GM	Mol. Cell. Biol.	1997
15314172	Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells Castoria, G, Migliaccio, A, Di Domenico, M, Lombardi, M, de Falco, A, Varricchio, L, Bilancio, A, Barone, MV, Auricchio, F	Mol. Cell. Biol.	2004
11889117	Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export Ishida, N, Hara, T, Kamura, T, Yoshida, M, Nakayama, K, Nakayama, KI	J. Biol. Chem.	2002
12904306	Estrogens down-regulate p27Kip1 in breast cancer cells through Skp2 and through nuclear export mediated by the ERK pathway Foster, JS, Fernando, RI, Ishida, N, Nakayama, KI, Wimalasena, J	J. Biol. Chem.	2003
8635462	Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells Migliaccio, A, Di Domenico, M, Castoria, G, de Falco, A, Bontempo, P, Nola, E, Auricchio, F	EMBO J.	1996
11726503	p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis Rodier, G, Montagnoli, A, Di Marcotullio, L, Coulombe, P, Draetta, GF, Pagano, M, Meloche, S	EMBO J.	2001
12093740	A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression Boehm, M, Yoshimoto, T, Crook, MF, Nallamshetty, S, True, A, Nabel, GJ, Nabel, EG	EMBO J.	2002
10831586	Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability Ishida, N, Kitagawa, M, Hatakeyama, S, Nakayama, K	J. Biol. Chem.	2000
9448290	Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1) Cheng, M, Sexl, V, Sherr, CJ, Roussel, MF	Proc. Natl. Acad. Sci. U.S.A.	1998
12814430	The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer Vermeulen, K, Van Bockstaele, DR, Berneman, ZN	Cell Prolif.	2003
9264403	Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway Kawada, M, Yamagoe, S, Murakami, Y, Suzuki, K, Mizuno, S, Uehara, Y	Oncogene	1997