The Growth-inhibtory Effect Of ZNF23 On Tumor Cells And Characterization Of Its Molecular Mechanism

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 growth. 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 growth inhibition by inducing G1 arrest and cell death. ZNF23 induced cell arrest in G1 phase through up-regulation of p27kip-1, but this process was p53-independent. ZNF23 promoted mitochrondrial cell death through down-regulation of Bcl-xL. Deletion analysis revealed that the effect of ZNF23 did not rely on its KRAB domain, but on the C-terminal zinc fingers. Furthermore, DNA binding sequence of ZNF23 was identified by BSS. Thus, ZNF23 is a new tumor-associated gene with growth-inhibitory ability and our work provides the basic foundation for future studies on the function of OKL38...