期刊
ONCOGENE
卷 21, 期 27, 页码 4220-4230出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205524
关键词
E2F; p14(ARF); MDM2; p53
资金
- MRC [G9400953] Funding Source: UKRI
- Cancer Research UK [13058] Funding Source: Medline
- Medical Research Council [G9400953] Funding Source: Medline
- Medical Research Council [G9400953] Funding Source: researchfish
The ARF protein product of the ink4a/arf locus is induced by a variety of oncogenic signals. ARF facilitates growth arrest through the p53 pathway by hindering the down-regulation of p53 activity mediated by MDM2, through the formation of a protein complex with MDM2. Here we have explored the possibility that human p14(LambdaRF) activity is integrated with growth regulating pathways other than p53, and report our results that p14(LambdaRF) can control the activity of the E217 transcription factor. p14(LambdaRF) regulates E2F activity in different cell-types, including p53(-/-)/mdm(-/-) MEFs, thus excluding that the effects of p14(LambdaRF) are indirectly caused through MDM2 modulation. p14(LambdaRF) down-regulates E2F-dependent transcription, and in cells undergoing E2F-dependent apoptosis prompts cell cycle arrest. p14(LambdaRF) possesses multiple binding domains for E2F-1, one of which resides within the N-terminal region and coincides with the regulation of E2F activity. A mutational analysis of p14(LambdaRF) indicates that the E2F-1 and MDM2 binding domains can be distinguished. These results highlight the potential interplay between p14(LambdaRF) and E2F, and establish p14(LambdaRF) as a pleiotrophic regulator of cell growth that acts by targetting at least two key pathways in the control of proliferation, namely E2F and p53.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据