Functional characterization of novel BTB/POZ-domain protein ZBTB8A

Abstract

[한글]

[영문]Human BTB/POZ proteins play important roles in the regulation of cell cycle, differentiation, and development. Some of the transcription factors with BTB/POZ domain have been identified as key regulators of oncogenesis. Previously, we found that the BTB/POZ proteins such as FBI-1, ZBTB2 and ZBTB5 regulate expression of the genes of the p53 pathway which is important in the regulation of cell cycle progression and proliferation. Recently, we noticed that a novel Kruppel-like zinc finger BTB domain-containing protein 8A (ZBTB8A) interacts with many other members of POK family proteins from the protein-protein interaction map of the BTB/POZ proteins, and isolated a cDNA encoding the ZBTB8A. The ZBTB8A consists of 441 amino acids and contains two C2H2 type zinc fingers. Interestingly, serial analysis of gene expression (SAGE) analysis showed that ZBTB8A is highly expressed in pancreatic cancer tissues. Over-expression of ZBTB8A in HEK293A cells represses transcription of the genes of p53 pathway, which include ARF, Hdm2, p53 and p21. MTT assays and FACS analysis showed that ZBTB8A stimulates cell proliferation and cell cycle progression. In particular, ZBTB8A repressed transcription of a cell cycle arrest gene p21 by binding to the proximal Sp1 binding elements (GC box 5/6) and the two distal p53-responsive elements. These results suggested that ZBTB8A is a transcription repressor of cell cycle arrest gene p21 and ZBTB8A may be a novel proto-oncogene stimulating cell proliferation.