Transcriptional regulation of AKT activation by E2F

Marie Chaussepied; Doron Ginsberg

doi:10.1016/j.molcel.2004.11.003

Transcriptional regulation of AKT activation by E2F

Marie Chaussepied, Doron Ginsberg

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

The pRB-E2F pathway is a downstream target of mitogenic signaling pathways. The E2F family of transcription factors has a pivotal role in regulating cell proliferation since it controls the timely expression of many genes that are required for cell cycle progression. Moreover, at least one member of this family, E2F1, can mediate apoptotic cell death. We show here that E2F also modulates the activity of a major signal transduction pathway: we demonstrate that E2F upregulates AKT activity through a transcription-dependent mechanism. We identify the adaptor protein Grb2associated binder 2 (Gab2) as a direct E2F target gene and an essential effector of E2F-dependent AKT activation. AKT activation was shown to inhibit E2F1induced apoptosis. Therefore, our results suggest the existence of a negative feedback loop involving E2F and AKT.

Original language	English
Pages (from-to)	831-837
Number of pages	7
Journal	Molecular Cell
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2004.11.003
State	Published - 3 Dec 2004
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to Yocheved Lamed for excellent technical assistance. We thank Avri Ben-Ze'ev, Atan Gross, Haihua Gu, Kristian Helin, Moshe Oren, Cheng-Kui Qu, Varda Rotter, and Yehiel Zick for the gift of reagents. We thank James DeGregori, Gordon Langsley, and Jonathan Weitzman for helpful discussions. This work was supported in part by grants from the Israel Cancer Research Fund (ICRF), Israel Science Foundation, and Yad Abraham Research Center for Diagnostics and Therapy, and by a postdoctoral fellowship from the Pasteur-Weizmann foundation to M.C. D.G. is an incumbent of the Recanati Career Development chair of Cancer research.

Funding

We are grateful to Yocheved Lamed for excellent technical assistance. We thank Avri Ben-Ze'ev, Atan Gross, Haihua Gu, Kristian Helin, Moshe Oren, Cheng-Kui Qu, Varda Rotter, and Yehiel Zick for the gift of reagents. We thank James DeGregori, Gordon Langsley, and Jonathan Weitzman for helpful discussions. This work was supported in part by grants from the Israel Cancer Research Fund (ICRF), Israel Science Foundation, and Yad Abraham Research Center for Diagnostics and Therapy, and by a postdoctoral fellowship from the Pasteur-Weizmann foundation to M.C. D.G. is an incumbent of the Recanati Career Development chair of Cancer research.

Funders	Funder number
Yad Abraham Research Center for Diagnostics and Therapy
Israel Cancer Research Fund
Israel Science Foundation

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title = "Transcriptional regulation of AKT activation by E2F",

abstract = "The pRB-E2F pathway is a downstream target of mitogenic signaling pathways. The E2F family of transcription factors has a pivotal role in regulating cell proliferation since it controls the timely expression of many genes that are required for cell cycle progression. Moreover, at least one member of this family, E2F1, can mediate apoptotic cell death. We show here that E2F also modulates the activity of a major signal transduction pathway: we demonstrate that E2F upregulates AKT activity through a transcription-dependent mechanism. We identify the adaptor protein Grb2associated binder 2 (Gab2) as a direct E2F target gene and an essential effector of E2F-dependent AKT activation. AKT activation was shown to inhibit E2F1induced apoptosis. Therefore, our results suggest the existence of a negative feedback loop involving E2F and AKT.",

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note = "Funding Information: We are grateful to Yocheved Lamed for excellent technical assistance. We thank Avri Ben-Ze'ev, Atan Gross, Haihua Gu, Kristian Helin, Moshe Oren, Cheng-Kui Qu, Varda Rotter, and Yehiel Zick for the gift of reagents. We thank James DeGregori, Gordon Langsley, and Jonathan Weitzman for helpful discussions. This work was supported in part by grants from the Israel Cancer Research Fund (ICRF), Israel Science Foundation, and Yad Abraham Research Center for Diagnostics and Therapy, and by a postdoctoral fellowship from the Pasteur-Weizmann foundation to M.C. D.G. is an incumbent of the Recanati Career Development chair of Cancer research. ",

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Transcriptional regulation of AKT activation by E2F

Abstract

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