HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, J. Articles by Fruman, D. A. Search for Related Content PubMed PubMed Citation Articles by Chen, J. Articles by Fruman, D. A.

FOXO Transcription Factors Cooperate with EF1 to Activate Growth Suppressive Genes in B Lymphocytes¹

Jing Chen^*, Isharat Yusuf^*, Hilde-Marie Andersen^* and David A. Fruman^2,

^* Department of Molecular Biology and Biochemistry, and Center for Immunology, University of California, Irvine, CA 92697

Forkhead transcription factors regulate many aspects of lymphocyte development and function. The FOXO subgroup of Forkhead factors opposes proliferation and survival, and FOXO inactivation is an important outcome of Ag receptor signaling. FOXO activity at target promoters is modulated by other transcription factors in a manner dependent on cell type and external stimulus. We have investigated the mechanisms by which FOXO proteins activate the promoters of two target genes in murine B lymphocytes, Ccng2 (encoding cyclin G₂) and Rbl2 (p130), each of which has been implicated in cell cycle arrest. FOXO proteins bound directly to both promoters in vitro and in vivo, augmented transcriptional activity in reporter assays, and increased expression of the endogenous genes. Each of the promoter sequences has consensus binding sites for the EF1 transcription factor, previously shown to either repress or activate different promoters. EF1 bound to the Ccng2 and Rbl2 promoters in vitro and in vivo and increased reporter activity as well as endogenous mRNA levels for these genes. Strikingly, EF1 synergized with FOXO proteins to strongly activate transcription from both promoters. Coexpression of EF1 enhanced FOXO-induced cell cycle arrest in B lymphoma cells. These findings establish a novel mechanism of FOXO function at target promoters: cooperation with EF1.

This article has been cited by other articles:

				T. Pew, M. Zou, D. R. Brickley, and S. D. Conzen Glucocorticoid (GC)-Mediated Down-Regulation of Urokinase Plasminogen Activator Expression via the Serum and GC Regulated Kinase-1/Forkhead Box O3a Pathway Endocrinology, May 1, 2008; 149(5): 2637 - 2645. [Abstract] [Full Text] [PDF]

				I. Yusuf, M. G. Kharas, J. Chen, R. Q. Peralta, A. Maruniak, P. Sareen, V. W. Yang, K. H. Kaestner, and D. A. Fruman KLF4 is a FOXO target gene that suppresses B cell proliferation Int. Immunol., May 1, 2008; 20(5): 671 - 681. [Abstract] [Full Text] [PDF]

				X.-F. Le, A. S. Arachchige-Don, W. Mao, M. C. Horne, and R. C. Bast Jr. Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells Mol. Cancer Ther., November 1, 2007; 6(11): 2843 - 2857. [Abstract] [Full Text] [PDF]

				K. L. Good and S. G. Tangye Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses PNAS, August 14, 2007; 104(33): 13420 - 13425. [Abstract] [Full Text] [PDF]

				R. M. Hinman, J. N. Bushanam, W. A. Nichols, and A. B. Satterthwaite B Cell Receptor Signaling Down-Regulates Forkhead Box Transcription Factor Class O 1 mRNA Expression via Phosphatidylinositol 3-Kinase and Bruton's Tyrosine Kinase J. Immunol., January 15, 2007; 178(2): 740 - 747. [Abstract] [Full Text] [PDF]

				M. G. Kharas, I. Yusuf, V. M. Scarfone, V. W. Yang, J. A. Segre, C. S. Huettner, and D. A. Fruman KLF4 suppresses transformation of pre-B cells by ABL oncogenes Blood, January 15, 2007; 109(2): 747 - 755. [Abstract] [Full Text] [PDF]