TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G(1)- to S-phase transition.
Although previous studies have implicated a role for TC1 (C8orf4) in cancer cell proliferation, the molecular mechanism of its action is still largely unclear. In this study, we showed, for the first time, that the mRNA levels of TC1 were upregulated by mitogens (FBS/thrombin) and at least partially, through the ERK1/2 signaling pathway. Interestingly, the over-expression of TC1 promoted the G(1)- to S-phase transition of the cell cycle, which was delayed by the deficiency of ERK1/2 signaling in fibroblast cells. Furthermore, the luciferase reporter assay indicated that the over-expression of TC1 significantly increased Cyclin D1 promoter-driven luciferase activity. Taken together, our findings revealed that TC1 was involved in the mitogen-activated ERK1/2 signaling pathway and positively regulated G(1)- to S-phase transition of the cell cycle. Our results may provide a novel mechanism of the role of TC1 in the regulation of cell proliferation.
Wang
Yi-Dong
YD
Core Facility of Gene Engineered Mouse, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, PR China.
Bian
Guo-Hui
GH
Lv
Xiao-Yan
XY
Zheng
Rong
R
Sun
Huan
H
Zhang
Zheng
Z
Chen
Ye
Y
Li
Qin-Wei
QW
Xiao
Yan
Y
Yang
Qiu-Tan
QT
Ai
Jian-Zhong
JZ
Wei
Yu-Quan
YQ
Zhou
Qin
Q
D000818:Animals; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016196:S Phase / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D005419:Flavonoids; D008934:Mitogens; D009363:Neoplasm Proteins; C418741:TCIM protein, human; C534905:Tcim protein, mouse; D019938:Cyclin D1; D008156:Luciferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013917:Thrombin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one