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General Comment |
Borud B, et al 2003 reported the cloning and Characterization of a Novel Zinc-finger Protein that Modulates
the Transcriptional Activity of Nuclear Receptors.
The orphan nuclear receptor Steroidogenic Factor-1 (SF-1) plays pivotal roles in the development
and function of steroidogenic organs. It transcriptionally regulates an array of factors required for
biosynthesis of steroid hormones and is also necessary for the expression of genes in the pituitary
and in the male reproductive tract. Here we describe the identification of a novel zinc-finger protein
that modifies the transcriptional potential of SF-1. This factor, which we call Zip67 (Zinc finger
protein 67 kDa), was cloned through a two-hybrid screen of a human testis cDNA library using the
C-terminal part of SF-1 as the bait. Transient transfection experiments demonstrated that Zip67
represses SF-1-dependent transcription, both in the context of multimerized SF-1 binding sites and
natural SF-1 inducible promoters. The interaction between Zip67 and SF-1 was dependent on an
intact activation function-2 (AF-2) domain of SF-1, and we propose a mechanism whereby Zip67
represses transcription through competition with p160 coactivators for binding to SF-1. Zip67 was
detected in SF-1 expressing tissues such as testis, adrenal, ovary and spleen in addition to other
tissues. In line with the broader expression pattern, we found that Zip67 also affected transcription
mediated by several other nuclear receptors. In conclusion, we have isolated a novel zinc-finger
protein that influences gene activation through interaction with the functionally important
AF-2-domain of nuclear receptors.
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