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Papers In Press, published online ahead of print March 13, 2001
Div. Immunol., Dept. Microbiol. Immunol., Inst. Med. Sci., Univ. Tokyo, Minato-ku, Tokyo 108-8639
Corresponding Author: takakis{at}ims.u-tokyo.ac.jp
The lck gene encodes a protein tyrosine kinase that plays a key role in signaling mediated through T cell receptor (TCR) and pre-TCR complexes. Transcription of the lck gene is regulated by two independent promoter elements; the proximal and distal promoters. Previous studies employing transgenic mice demonstrated that the sequence between -584 and -240 from the transcription start site in the mouse lck proximal promoter is required for its tissue-specific expression in the thymus. In this study, we demonstrate that a Krüppel-like zinc finger protein, mt-beta (BFCOL1, BERF-1, ZBP-89, ZNF148), previously cloned as a protein that binds to the CD3-delta gene enhancer, binds to the -365 to -328 region of the lck proximal promoter. Mt-beta is ubiquitously expressed in various cell lines and mouse tissues. Overexpressed mt-beta is more active in T-lineage cells than B-lineage cells for transactivating an artificial promoter consisting of the mt-beta binding site and a TATA box. Activity of the lck proximal promoter was significantly impaired by mutating the mt-beta binding site or by reducing mt-beta protein expression level by using antisense mRNA. Our results indicate that mt-beta activity is regulated in a tissue-specific manner, and that mt-beta is a critical transactivator for the lck proximal promoter.
J. Biol. Chem, 10.1074/jbc.M008387200
Submitted on September 13, 2000
Revised on February 19, 2001
Accepted on March 12, 2001
Identification and characterization of a transcriptional regulator for the lck proximal promoter
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