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Nucleic Acids Research, Vol 25, Issue 24 5025-5032, Copyright © 1997 by Oxford University Press

ARTICLES

HUB1, a novel Kruppel type zinc finger protein, represses the human T cell leukemia virus type I long terminal repeat-mediated expression

K Okumura, G Sakaguchi, K Naito, T Tamura and H Igarashi
Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu, Osaka 566, Japan.

We have shown that human T-cell leukemia virus type I (HTLV-I) gene expression is negatively regulated by the U5 repressive element (U5RE) of its long terminal repeat (LTR). To isolate factors binding to U5RE, we screened a cDNA expression library by south-western blotting with a U5RE probe. Screening 2 x10(6) clones gave a positive clone with a 3.8 kb insert encoding a novel 671 residue polypeptide, named HTLV-I U5RE binding protein 1 (HUB1), with five zinc finger domains and a Kruppel- associated box like domain; HUB1 may be related to a repressor belonging to the Kruppel type zinc finger protein. A 4.0 kb mRNA for HUB1 is ubiquitously expressed among all human tissues tested. HUB1 recognizes the TCCACCCC sequence as a core motif and exerts a strong repressive effect on HTLV-I LTR-mediated expression. A new repressive domain, named HUB1 repressive (HUR) domain, was identified, rather than the Kruppel-associated box like domain. The N-terminal region upstream of HUR domain seemed to be also indispensable to the repression. Thus, we propose that HUB1 is a new type repressor and plays an important role in the HTLV-I U5-mediated repression.
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