Lichtenberg U, Quintrell N, Bishop J M
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Oncogene. 1992 May;7(5):849-58.
The vertebrate gene HCK encodes a protein-tyrosine kinase that is closely related to the product of the proto-oncogene SRC. HCK is expressed principally in monocytic and granulocytic hematopoietic cells, in coordination with differentiation of these cells. Here we report an initial description of the mechanisms by which expression of human HCK is controlled. Induction of the gene during differentiation was manifested by an increase in the steady-state levels of HCK RNA and protein product. The accumulation of RNA apparently resulted from modulation of transcription itself, since no change occurred in the stability of the transcripts. Transcription initiated at multiple sites, clustered c. 145 nucleotides upstream of the first intron of HCK. The sequence of 660 bp upstream of the major initiation site was determined, revealing candidate binding sites for Sp1 and AP-2 transcription factors, but neither TATA nor CAAT elements. Comparison to the same region of the mouse hck locus showed five small regions of similarity, only two of which were topographically analogous between the two sequences. It appears that expression of HCK is regulated primarily through control of transcription, but the mechanisms by which tissue-specific expression and increase of transcription during differentiation are achieved remain to be explored.
脊椎动物基因HCK编码一种蛋白酪氨酸激酶，它与原癌基因SRC的产物密切相关。HCK主要在单核细胞和粒细胞造血细胞中表达，与这些细胞的分化协同进行。在此，我们报告了人类HCK表达调控机制的初步描述。在分化过程中该基因的诱导表现为HCK RNA和蛋白质产物稳态水平的增加。RNA的积累显然是由于转录本身的调节，因为转录本的稳定性没有变化。转录起始于多个位点，聚集在HCK第一个内含子上游约145个核苷酸处。确定了主要起始位点上游660 bp的序列，揭示了Sp1和AP-2转录因子的候选结合位点，但没有TATA元件和CAAT元件。与小鼠hck基因座的相同区域比较显示有五个小的相似区域，其中只有两个在两个序列之间在拓扑结构上相似。看来HCK的表达主要通过转录控制来调节，但在分化过程中实现组织特异性表达和转录增加的机制仍有待探索。
