Stem Cells
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


First published online June 28, 2007
Stem Cells Vol. 25 No. 10 October 2007, pp. 2439 -2447
doi:10.1634/stemcells.2007-0207; www.StemCells.com
© 2007 AlphaMed Press

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
2007-0207v1
25/10/2439    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kikuchi, J.
Right arrow Articles by Furukawa, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kikuchi, J.
Right arrow Articles by Furukawa, Y.

TISSUE-SPECIFIC STEM CELLS

E2F-6 Suppresses Growth-Associated Apoptosis of Human Hematopoietic Progenitor Cells by Counteracting Proapoptotic Activity of E2F-1

Jiro Kikuchia, Rumi Shimizua, Taeko Wadaa, Hidenobu Andob, Mitsuru Nakamurab, Keiya Ozawac, Yusuke Furukawaa,c

aDivision of Stem Cell Regulation, Center for Molecular Medicine, and
cDivision of Hematology, Department of Internal Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan; and
bCell Regulation Analysis Team, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan

Key Words. E2F • Hematopoietic progenitor cell • Apoptosis • Transcription

Correspondence: Yusuke Furukawa, M.D., Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-City, Tochigi 329-0498, Japan. Telephone: 81-285-58-7400; Fax: 81-285-44-7501; e-mail: furuyu{at}jichi.ac.jp

Received March 27, 2007; accepted for publication June 18, 2007.
First published online in STEM CELLS EXPRESS   June 28, 2007.



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.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
STEM CELLS THE ONCOLOGIST CME ALPHAMED PRESS JOURNALS

Copyright © 2007 by AlphaMed Press.