The gene structure and promoter analysis of mouse lymphocyte signal transduction molecule alpha 4 that is related to the yeast TAP42 involved in a rapamycin-sensitive pathway.

ABSTRACT

The mouse alpha 4 phosphoprotein encoding a component associated with the B cell antigen receptor (BCR)-mediated signal transduction is suggested to be involved in a unique rapamycin-sensitive pathway. We studied the structure and the molecular mechanism of the expression of alpha 4 gene by isolating two phage clones, named #10 and #23, covering entire exons of the mouse alpha 4 gene. The alpha 4 gene is located within about 25 kb and composed of six exons. To analyze the regulation of alpha 4 gene expression, we determined the nucleotide sequence toward 2 kb upstream of the translation start site of the alpha 4 gene. The 5'-flanking region does not contain a typical TATA box or the initiation consensus sequence, but it contains a CCAAT box, E-boxes, and several DNA binding motifs such as c-Myc, c-Myb, and c-Ets. Transcription of the alpha 4 gene starts at four different sites, determined by primer extension analysis, that were surrounded by Y-rich sequences. We further characterized the functional promoter of the alpha 4 gene at the region between -263 and the transcription start site of alpha 4 gene by luciferase assay system and suggested that the 5' upstream region of alpha 4 gene contains the silencer element of MT repetitive sequence.