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TM4SF5 accelerates G1/S phase progression via cytosolic p27(Kip1) expression and RhoA activity

Cited 24 time in Web of Science Cited 24 time in Scopus
Authors

Kim, Hyeonjung; Kang, Minkyung; Lee, Sin-Ae; Kwak, Tae Kyoung; Jung, Oisun; Lee, Hyo Jeong; Kim, Sung-Hoon; Lee, Jung Weon

Issue Date
2010-08
Publisher
Elsevier BV
Citation
Biochimica et Biophysica Acta - Molecular Cell Research, Vol.1803 No.8, pp.975-982
Abstract
Transmembrane 4 L six family member 5 (TM4SF5) causes epithelial mesenchymal transition (EMT) for aberrant cell proliferation. However, the effects of TM4SF5 expression on cell cycle are unknown so far. In this study, using hepatocytes that either ectopically or endogenously express TM4SF5 and human hepatocarcinoma tissues, the role of TM4SF5 in G1/S phase progression was examined. We found that TM4SF5 expression accelerated G1/S phase progression with facilitated cyclin D1 and E expression and Rb phosphorylation. Furthermore, TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. However, TM4SF5-facilitated G1/S phase progression was blocked by silencing of p27(Kip1) using siRNA or by infection of active RhoA. Pharmacological inhibition of ROCK accelerated the G1/S phase progression of control TM4SF5-unexpressing cells. Altogether, these observations suggest that TM4SF5 accelerates G1/S phase progression with facilitated CDK4/cyclin D1 entry into the nucleus, which might be supported by TM4SF5-mediated actin reorganization through cytosolic p27(Kip1) expression and Rho GTPase activity. (c) 2010 Elsevier B.V. All rights reserved.
ISSN
0167-4889
Language
English
URI
https://hdl.handle.net/10371/82062
DOI
https://doi.org/10.1016/j.bbamcr.2010.04.001
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