The TRIP-Br family of transcriptional regulators is essential for the execution of cyclin E-mediated cell cycle progression.
The G1 D-type cyclins, in conjunction with cyclin-dependent kinases Cdk4 and Cdk6, play key roles in the execution of mitogen-induced cellular proliferation. TRIP-Br1, a member of the TRIP-Br family of transcriptional regulators, has been implicated in the regulation of Cdk4/cyclin D activity. To further elucidate the functional role(s) of the TRIP-Br proteins in mitogenic signaling, we have developed the synthetic DNA enzymes E-Br1 and E-Br2 to specifically knock down the serum-inducible expression of TRIP-Br1 and TRIP-Br2, respectively, in WI-38 human fibroblasts in culture, as well as generated TRIP-Br2 null primary embryonic fibroblasts from a novel TRIP-Br2 knockout mouse model. Both strategies consistently reveal that ablation of TRIP-Br1 or TRIP-Br2 expression disrupts mitogenic signaling in a manner that suppresses serum-induced cyclin E expression, S-phase entry and cellular proliferation. We conclude that both TRIP-Br1 and TRIP-Br2 are required for proper transduction of mitogenic signals and execution of serum-inducible cell cycle progression.
Sim
Khe Guan
KG
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore.
Cheong
Jit Kong
JK
Hsu
Stephen I-Hong
SI
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D056741:Cyclin D; D019927:Cyclin E / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D000092468:Bromodomain Containing Proteins
D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D021881:DNA, Catalytic; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C402464:SERTAD1 protein, human; C426827:SERTAD2 protein, human; D000092468:Bromodomain Containing Proteins; C486065:Sertad2 protein, mouse