| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Catenin Pathway
* Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL 60612;
Ludwig Institute for Cancer Research, Lausanne Branch and University of Lausanne, Epalinges, Switzerland; and
Hubrecht Laboratory, Center for Biomedical Genetics, Utrecht, The Netherlands
By interacting with MHC class II molecules, CD4 facilitates lineage development as well as activation of Th cells. Expression of physiological levels of CD4 requires a proximal CD4 enhancer to stimulate basic CD4 promoter activity. T cell factor (TCF)-1/
-catenin pathway has previously been shown to regulate thymocyte survival via up-regulating antiapoptotic molecule Bcl-xL. By both loss and gain of function studies, in this study we show additional function of TCF-1/-catenin pathway in the regulation of CD4 expression in vivo. Mice deficient in TCF-1 displayed significantly reduced protein and mRNA levels of CD4 in CD4+CD8+ double-positive (DP) thymocytes. A transgene encoding Bcl-2 restored survival but not CD4 levels of TCF-1–/– DP cells. Thus, TCF-1-regulated survival and CD4 expression are two separate events. In contrast, CD4 levels were restored on DP TCF-1–/– cells by transgenic expression of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain required for interacting with -catenin. Furthermore, forced expression of a stabilized -catenin, a coactivator of TCF-1, resulted in up-regulation of CD4. TCF-1 or stabilized -catenin greatly stimulated activity of a CD4 reporter gene driven by a basic CD4 promoter and the CD4 enhancer. However, mutation of a potential TCF binding site located within the enhancer abrogated TCF-1 and -catenin-mediated activation of CD4 reporter. Finally, recruitment of TCF-1 to CD4 enhancer was detected in wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysis. Thus, our results demonstrated that TCF/-catenin pathway enhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity.
This article has been cited by other articles:
|
|
 |
|
  Z. Huang, R. Wang, H. Xie, W. Shang, S. Manicassamy, and Z. Sun Stabilized {beta}-Catenin Potentiates Fas-Mediated T Cell Apoptosis J. Immunol., May 15, 2008; 180(10): 6586 - 6592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yu, M. Wan, J. Zhang, J. Wu, R. Khatri, and T. Chi Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development PNAS, March 11, 2008; 105(10): 3873 - 3878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Aliahmad and J. Kaye Development of all CD4 T lineages requires nuclear factor TOX J. Exp. Med., January 21, 2008; 205(1): 245 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Jeannet, M. Scheller, L. Scarpellino, S. Duboux, N. Gardiol, J. Back, F. Kuttler, I. Malanchi, W. Birchmeier, A. Leutz, et al. Long-term, multilineage hematopoiesis occurs in the combined absence of -catenin and {gamma}-catenin Blood, January 1, 2008; 111(1): 142 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Melichar, K. Narayan, S. D. Der, Y. Hiraoka, N. Gardiol, G. Jeannet, W. Held, C. A. Chambers, and J. Kang Regulation of {gamma}{delta} Versus {alpha}{beta} T Lymphocyte Differentiation by the Transcription Factor SOX13 Science, January 12, 2007; 315(5809): 230 - 233. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
