E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1.

E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Research Abstract Details 

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E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Abstract Text:

Jiro Kikuchi,Rumi Shimizu,Taeko Wada,Hidenobu Ando,Mitsuru Nakamura,Keiya Ozawa,Yusuke Furukawa,Jiro Kikuchi,Rumi Shimizu,Taeko Wada,Hidenobu Ando,Mitsuru Nakamura,Keiya Ozawa,Yusuke Furukawa,Jiro Kikuchi,Rumi Shimizu,Taeko Wada,Hidenobu Ando,Mitsuru Nakamura,Keiya Ozawa,Yusuke Furukawa,

E2F-6 is a dominant-negative transcriptional repressor against other members of the E2F family. In this study, we investigated the expression and function of E2F-6 in human hematopoietic progenitor cells to clarify its role in hematopoiesis. We found that among E2F subunits, E2F-1, E2F-2, E2F-4, and E2F-6 were expressed in CD34(+) human hematopoietic progenitor cells. The expression of E2F-6 increased along with proliferation and decreased during differentiation of hematopoietic progenitors, whereas the other three species were upregulated in CD34(-) bone marrow mononuclear cells. Overexpression of E2F-6 did not affect the growth of immature hematopoietic cell line K562 but suppressed E2F-1-induced apoptosis, whereas it failed to inhibit apoptosis induced by differentiation inducers and anticancer drugs. Among E2F-1-dependent apoptosis-related molecules, E2F-6 specifically inhibited upregulation of Apaf-1 by competing with E2F-1 for promoter binding. E2F-6 similarly suppressed apoptosis and Apaf-1 upregulation in primary hematopoietic progenitor cells during cytokine-induced proliferation but had no effect when they were differentiated. As a result, E2F-6 enhanced the clonogenic growth of colony-forming unit-granulocyte, erythroid, macrophage, and megakaryocyte. These results suggest that E2F-6 provides a failsafe mechanism against loss of hematopoietic progenitor cells during proliferation. Disclosure of potential conflicts of interest is found at the end of this article.

E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Publishing Authors By Initials

J Kikuchi,R Shimizu,T Wada,H Ando,M Nakamura,K Ozawa,Y Furukawa,J Kikuchi,R Shimizu,T Wada,H Ando,M Nakamura,K Ozawa,Y Furukawa,J Kikuchi,R Shimizu,T Wada,H Ando,M Nakamura,K Ozawa,Y Furukawa,

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E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Stem cells (Dayton, Ohio)

VOLUME: 25

Page Numbers: 2439-47

Journal Abbreviation: Stem Cells

ISSN: 1549-4918

DAY: 28

MONTH: 06

YEAR: 2007

E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Information

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LANGUAGE: eng

NlmUniqueID: 9304532

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AFFILIATION: Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-City, Tochigi 329-0498, Japan.

Country: United States

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MEDLINETA: Stem Cells

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