RRC ID 56154
著者 Komori H, Goto Y, Kurayoshi K, Ozono E, Iwanaga R, Bradford AP, Araki K, Ohtani K.
タイトル Differential requirement for dimerization partner DP between E2F-dependent activation of tumor suppressor and growth-related genes.
ジャーナル Sci Rep
Abstract 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.
巻・号 8(1)
ページ 8438
公開日 2018-5-31
DOI 10.1038/s41598-018-26860-0
PII 10.1038/s41598-018-26860-0
PMID 29855511
PMC PMC5981219
MeSH ADP-Ribosylation Factors / genetics ADP-Ribosylation Factors / metabolism Apoptosis Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Dimerization E2F1 Transcription Factor / chemistry E2F1 Transcription Factor / genetics E2F1 Transcription Factor / metabolism* Fibroblasts / cytology Fibroblasts / metabolism Humans Promoter Regions, Genetic RNA Interference RNA, Small Interfering / metabolism Transcription Factor DP1 / antagonists & inhibitors Transcription Factor DP1 / genetics Transcription Factor DP1 / metabolism* Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism Tumor Suppressor Protein p53 / metabolism*
IF 4.011
引用数 2
リソース情報
ヒト・動物細胞 WI-38(RCB0702)