Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression.

The Krupple-associated box-containing zinc-finger proteins (KRAB-ZFPs) make up one of the largest family of transcription factors. Several members of the KRAB-ZFPs modulate cell growth, survival and are implicated in malignant disorders. However, most members are not well characterized and their functions are largely unknown. Here we report that ZNF23, a member of KRAB-ZFPs, inhibits cell cycle progression. ZNF23 protein localized to the nucleus and was ubiquitously expressed in all tested normal tissues. However, the expression levels of ZNF23 protein were lost or greatly reduced in human cancer. Ectopic expression of ZNF23 led to enhancement of p27(kip-1) expression, growth inhibition and cell cycle arrest in G(1) phase. Downregulation of p27(kip-1) by siRNA against p27(kip-1) reversed growth inhibition induced by ZNF23. Furthermore, the growth-inhibitory effect of ZNF23 was p53-independent. Deletion analysis revealed that the effect of ZNF23 did not rely on its KRAB domain, but on the C-terminal zinc fingers. Thus, we have identified a new member of KRAB-ZNF superfamily with growth-inhibitory ability and its downregulation may contribute to carcinogenesis.

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