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 Email this article to a friend 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 Rao, S. Articles by Simon, M. C. Search for Related Content PubMed PubMed Citation Articles by Rao, S. Articles by Simon, M. C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 16, 11115-11124, April 16, 1999

SPI-B Activates Transcription via a Unique Proline, Serine, and Threonine Domain and Exhibits DNA Binding Affinity Differences from PU.1

Sridhar Rao, Amy Matsumura^¶, Jung Yoon^¶, and M. Celeste Simon^¶

From the  Department of Pathology, ^¶ Howard Hughes Medical Institute, and  Departments of Medicine and Molecular Genetics and Cell Biology, the University of Chicago, Chicago, Illinois 60637

SPI-B is a B lymphocyte-specific Ets transcription factor that shares a high degree of similarity with PU.1/SPI-1. In direct contrast to PU.1^/ mice that die in utero and lack monocytes, neutrophils, B cells, and T cells, Spi-B^/ mice are viable and exhibit a severe B cell proliferation defect. Since PU.1 is expressed at wild type levels in Spi-B^/ B cells, the mutant mice provide genetic evidence that SPI-B and PU.1 have at least some non-redundant roles in B lymphocytes. To begin to understand the molecular basis for these defects, we delineated functional domains of SPI-B for comparison to those of PU.1. By using a heterologous co-transfection system, we identified two independent transactivation domains in the N terminus of SPI-B. Interestingly, only one of these domains (amino acids 31-61), a proline/serine/threonine-rich region, unique among Ets proteins, is necessary for transactivation of the immunoglobulin  light chain enhancer. This transactivation motif is in marked contrast to PU.1, which contains acidic and glutamine-rich domains. In addition, we describe a functional PU.1 site within the c-FES promoter which SPI-B fails to bind efficiently and transactivate. Finally, we show that SPI-B interacts with the PU.1 cofactors Pip, TBP, c-Jun and with lower affinity to nuclear factor interleukin-6 and retinoblastoma. Taken together, these data suggest that SPI-B binds DNA with a different affinity for certain sites than PU.1 and harbors different transactivation domains. We conclude that SPI-B may activate unique target genes in B lymphocytes and interact with unique, although currently unidentified, cofactors.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R. Dahl, S. R. Iyer, K. S. Owens, D. D. Cuylear, and M. C. Simon The Transcriptional Repressor GFI-1 Antagonizes PU.1 Activity through Protein-Protein Interaction J. Biol. Chem., March 2, 2007; 282(9): 6473 - 6483. [Abstract] [Full Text] [PDF]

				C.-d. Geng and W. V. Vedeckis c-Myb and Members of the c-Ets Family of Transcription Factors Act as Molecular Switches to Mediate Opposite Steroid Regulation of the Human Glucocorticoid Receptor 1A Promoter J. Biol. Chem., December 30, 2005; 280(52): 43264 - 43271. [Abstract] [Full Text] [PDF]

				J. M. Lefebvre, M. C. Haks, M. O. Carleton, M. Rhodes, G. Sinnathamby, M. C. Simon, L. C. Eisenlohr, L. A. Garrett-Sinha, and D. L. Wiest Enforced Expression of Spi-B Reverses T Lineage Commitment and Blocks {beta}-Selection J. Immunol., May 15, 2005; 174(10): 6184 - 6194. [Abstract] [Full Text] [PDF]

				T.-G. Kim, J. C. Kraus, J. Chen, and Y. Lee JUMONJI, a Critical Factor for Cardiac Development, Functions as a Transcriptional Repressor J. Biol. Chem., October 24, 2003; 278(43): 42247 - 42255. [Abstract] [Full Text] [PDF]

				M. K. Anderson, X. Sun, A. L. Miracle, G. W. Litman, and E. V. Rothenberg Evolution of hematopoiesis: Three members of the PU.1 transcription factor family in a cartilaginous fish, Raja eglanteria PNAS, January 5, 2001; (2001) 21478998. [Abstract] [Full Text]

				S. Rao, L. A. Garrett-Sinha, J. Yoon, and M. C. Simon The Ets Factors PU.1 and Spi-B Regulate the Transcription in Vivo of P2Y10, a Lymphoid Restricted Heptahelical Receptor J. Biol. Chem., November 26, 1999; 274(48): 34245 - 34252. [Abstract] [Full Text] [PDF]

				M. K. Anderson, X. Sun, A. L. Miracle, G. W. Litman, and E. V. Rothenberg Evolution of hematopoiesis: Three members of the PU.1 transcription factor family in a cartilaginous fish, Raja eglanteria PNAS, January 16, 2001; 98(2): 553 - 558. [Abstract] [Full Text] [PDF]