CHARACTERIZATION OF HUCRBP (YY1, NF-E1, DELTA) - A TRANSCRIPTION FACTOR THAT BINDS THE REGULATORY REGIONS OF MANY VIRAL AND CELLULAR GENES

被引:63
作者
BECKER, KG
JEDLICKA, P
TEMPLETON, NS
LIOTTA, L
OZATO, K
机构
[1] NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892
[2] NCI,PATHOL LAB,BETHESDA,MD 20892
关键词
ZINC FINGER; DNA BINDING; PHOSPHOPROTEIN; ACTIVATOR; REPRESSOR;
D O I
10.1016/0378-1119(94)90435-9
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The UCRBP (YY1, delta, NF-E1) protein has been isolated for its ability to bind to the UCR (upstream conserved region) site present in the conserved murine leukemia virus long terminal repeat. UCRBP carries a highly charged N-terminal domain and four C2-H2-type zinc fingers at its C-terminal end. The present study reveals the following results: (i) The UCR site is present in the upstream and/or regulatory regions of numerous mammalian cellular and viral genes to which both recombinant and cellular UCRBP bind. UCR sites are also found in the regulatory regions of repetitive sequences including human LINE-1 elements and mouse intracisternal-A particle sequences. (ii) By immuuological and UV cross-linking experiments, we found that two proteins, of approx. 68 kDa and an antigenically related protein of approx. 40 kDa, account for much of the UCR-binding activity in T-lymphocytes. (iii) There is evidence that UCRBP acts as it phosphoprotein. Eight consensus phosphorylation bites are found rn the deduced amino-acid sequence of human UCRB. The cellular UCR-binding activity was abolished by phosphatase treatment, and there is an incremental increase in apparent molecular mass between the cytoplasmic and nuclear forms of the protein, suggesting phosphorylation. (iv) Although UCRBP has been previously shown to act as a transcriptional repressor, we show here that UCRBP can also act as a positive transactivator of a reporter driven by UCR elements when used in co-transfection assays, This transactivation occurred in a dose-restricted manner and was absent at high concentrations of a UCRBP expression plasmid, indicating a complex mode of function. Taken together, these results indicate that a very large number of cellular and viral genes are controlled by UCRBP, whose function is manifested in both a positive and negative manner.
引用
收藏
页码:259 / 266
页数:8
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