ZBTB48
Description
The ZBTB48 (zinc finger and BTB domain containing 48) is a protein-coding gene located on chromosome 1.
ZBTB48, also known as TZAP, is a protein that directly binds to the double-stranded repeat sequence of telomeres. It is encoded by the ZBTB48 gene in humans. Loss of ZBTB48 leads to telomere elongation in cells with both long and short telomeres. Overexpression of ZBTB48 in cancer cells using the Alternative Lengthening of Telomeres (ALT) mechanism results in telomere trimming. Beyond its telomeric function, ZBTB48 acts as a transcriptional activator for a small set of target genes, including MTFP1 and CDKN2A. ZBTB48 is located on chromosome 1p36, a region frequently rearranged (leiomyoma & leukaemia) or deleted (neuroblastoma, melanoma, Merkel cell carcinoma, pheochromocytoma, and carcinomas of colon and breast) in various human cancers. This suggests that ZBTB48 might be a putative tumor suppressor, although this remains under debate.
ZBTB48 is a telomere-binding protein that regulates telomere length by directly binding to the double-stranded 5'-TTAGGG-3' repeat sequence at telomeres. It preferentially binds to telomeres with low shelterin complex concentration and initiates telomere trimming, preventing the accumulation of abnormally long telomeres. ZBTB48 also functions as a transcription regulator, binding to promoter regions and regulating the expression of a small subset of genes, including MTFP1. It regulates the expression of the J and/or S elements in the MHC II promoter and acts as a negative regulator of cell proliferation by specifically activating the expression of ARF, a tumor suppressor isoform of CDKN2A.
ZBTB48 is also known as HKR3, TZAP, ZNF855, pp9964.
