CDKN1B is phosphorylated in response to estrogen

Stable Identifier
R-HSA-9632868
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of UHMK1 [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created