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Atypical E2Fs: new players in the E2F transcription factor family.

ABSTRACT: As major regulators of the cell cycle, apoptosis and differentiation, E2F transcription factors have been studied extensively in a broad range of organisms. The recent identification of atypical E2F family members further expands our structural, functional and molecular view of the cellular E2F activity. Unlike other family members, atypical E2Fs have a duplicated DNA-binding domain and control gene expression without heterodimerization with dimerization partner proteins. Recently, knockout strategies in plants and mammals have pinpointed that atypical E2Fs have a crucial role in plant cell size control, endocycle regulation, proliferation and apoptotic response upon DNA stress. Their position at the crossroads of proliferation and DNA stress response marks these novel E2F proteins as interesting study objects in the field of tumor biology.

SUBMITTER: Lammens T

PROVIDER: S-EPMC2808192 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Atypical E2Fs: new players in the E2F transcription factor family.

Lammens Tim T Li Jing J Leone Gustavo G De Veylder Lieven L

Trends in cell biology 20090207 3

As major regulators of the cell cycle, apoptosis and differentiation, E2F transcription factors have been studied extensively in a broad range of organisms. The recent identification of atypical E2F family members further expands our structural, functional and molecular view of the cellular E2F activity. Unlike other family members, atypical E2Fs have a duplicated DNA-binding domain and control gene expression without heterodimerization with dimerization partner proteins. Recently, knockout stra ...[more]

PMID: 19201609

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E2F-5, a new E2F family member that interacts with p130 in vivo.

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Prognostic Value of E2F Transcription Factor Expression in Pancreatic Adenocarcinoma.

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| S-EPMC8611937 | biostudies-literature

Atypical E2fs control lymphangiogenesis through transcriptional regulation of Ccbe1 and Flt4.

Project description:Lymphatic vessels are derived from venous endothelial cells and their formation is governed by the Vascular endothelial growth factor C (VegfC)/Vegf receptor 3 (Vegfr3; Flt4) signaling pathway. Recent studies show that Collagen and Calcium Binding EGF domains 1 protein (Ccbe1) enhances VegfC-dependent lymphangiogenesis. Both Ccbe1 and Flt4 have been shown to be indispensable for lymphangiogenesis. However, how these essential players are transcriptionally regulated remains poorly understood. In the case of angiogenesis, atypical E2fs (E2f7 and E2f8) however have been recently shown to function as transcriptional activators for VegfA. Using a genome-wide approach we here identified both CCBE1 and FLT4 as direct targets of atypical E2Fs. E2F7/8 directly bind and stimulate the CCBE1 promoter, while recruitment of E2F7/8 inhibits the FLT4 promoter. Importantly, inactivation of e2f7/8 in zebrafish impaired venous sprouting and lymphangiogenesis with reduced ccbe1 expression and increased flt4 expression. Remarkably, over-expression of e2f7/8 rescued Ccbe1- and Flt4-dependent lymphangiogenesis phenotypes. Together these results identified E2f7/8 as novel in vivo transcriptional regulators of Ccbe1 and Flt4, both essential genes for venous sprouting and lymphangiogenesis.

| S-EPMC3771987 | biostudies-literature

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