Differential requirement for dimerization partner DP between E2F-dependent activation of tumor suppressor and growth-related genes.

Autor:	Komori H; Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI, 48109-2216, USA., Goto Y; Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan., Kurayoshi K; Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan., Ozono E; Chromosome Replication Lab, The Francis Crick Institute, Midland Road, London, NW1 1AT, UK., Iwanaga R; Department of Craniofacial Biology, University of Colorado School of Dental Medicine, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA., Bradford AP; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 2800 East 19th Avenue, Aurora, CO, 80045, USA., Araki K; Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan., Ohtani K; Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan. btm88939@kwansei.ac.jp.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 May 31; Vol. 8 (1), pp. 8438. Date of Electronic Publication: 2018 May 31.
DOI:	10.1038/s41598-018-26860-0
Abstrakt:	The transcription factor E2F plays crucial roles in cell proliferation and tumor suppression by activating growth-related genes and pro-apoptotic tumor suppressor genes, respectively. It is generally accepted that E2F binds to target sequences with its heterodimeric partner DP. Here we show that, while knockdown of DP1 expression inhibited ectopic E2F1- or adenovirus E1a-induced expression of the CDC6 gene and cell proliferation, knockdown of DP1 and DP2 expression did not affect ectopic E2F1- or E1a-induced expression of the tumor suppressor ARF gene, an upstream activator of the tumor suppressor p53, activation of p53 or apoptosis. These observations suggest that growth related and pro-apoptotic E2F targets are regulated by distinct molecular mechanisms and contradict the threshold model, which postulates that E2F activation of pro-apoptotic genes requires a higher total activity of activator E2Fs, above that necessary for E2F-dependent activation of growth-related genes.
Databáze:	MEDLINE
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