Abstract
Human BTB/POZ proteins play important roles in the regulation of cell cycle, differentiation, and development. Some transcription factors with BTB/POZ domain have been identified as a key regulatory gene of cancer development. Previously, we found that BTB/POZ proteins such as FBI‐1, ZBTB2 and ZBTB5 regulate expression of the genes of p53 pathway important in the regulation of cell cycle. Recently, we isolated a cDNA encoding a new Krüppel‐like zinc finger BTB domain‐containing protein 8A (ZBTB8A). The ZBTB8A consists of 441 amino acids and contains two C2H2 type zinc fingers. 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 genes, which include ARF, MDM2, p53 and p21. In particular, ZBTB8A potently represses transcription of p21 gene through the distal p53 binding element. FACS and MTT assays show that ZBTB8A stimulates cell proliferation and cell cycle progression. These results suggest that ZBTB8A may be a potential proto‐oncogene.
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