Zbtb5, short for zinc finger and BTB domain-containing 5, is a proto-oncogene. It is involved in regulating cell fate decisions, especially those related to c-Myc. Zbtb5 represses p21/CDKN1A, a cell cycle arrest gene, by competing with p53 and recruiting corepressor histone deacetylase complexes, thus promoting cell proliferation [1,2].

In terms of cell fate, c-Myc directly activates Zbtb5 transcription. In the absence of p53, Zbtb5 is acetylated at K597 by interacting with p300, and then activates NOXA transcription to induce apoptosis. Conversely, in the presence of p53, Zbtb5 interacts with p53, blocking its acetylation at K597. The non-acetylated Zbtb5 then interacts with mSin3A/HDAC1 to repress p21/CDKN1A transcription and promote cell proliferation [1].

In conclusion, Zbtb5 is a key factor in cell fate decisions, acting as a switch between cell proliferation and apoptosis, regulated by c-Myc, p53, and p300. Understanding Zbtb5's role can provide insights into cancer development, as its abnormal regulation may lead to uncontrolled cell growth or inappropriate apoptosis evasion [1].

References:

1. Choi, Seo-Hyun, Koh, Dong-In, Ahn, Haemin, Kim, Youngsoo, Hur, Man-Wook. 2020. Cell fate decisions by c-Myc depend on ZBTB5 and p53. In Biochemical and biophysical research communications, 533, 1247-1254. doi:10.1016/j.bbrc.2020.09.137. https://pubmed.ncbi.nlm.nih.gov/33051058/

2. Koh, Dong-In, Choi, Won-Il, Jeon, Bu-Nam, Yun, Chae-Ok, Hur, Man-Wook. 2009. A novel POK family transcription factor, ZBTB5, represses transcription of p21CIP1 gene. In The Journal of biological chemistry, 284, 19856-66. doi:10.1074/jbc.M109.025817. https://pubmed.ncbi.nlm.nih.gov/19491398/