Cell fate decisions by c-Myc depend on ZBTB5 and p53.
The oncoprotein, c-Myc, not only promotes cell proliferation, but can also induce or sensitize cells to apoptosis. However, how c-Myc decides cell fate and which c-Myc downstream target genes are involved remain unknown. Previously, we showed that ZBTB5 (zinc finger and BTB domain-containing 5) is a proto-oncogene that stimulates cell proliferation. ZBTB5 represses p21/CDKN1A by competing with p53 and recruiting corepressor histone deacetylase complexes. Herein, we found that c-Myc directly activates the transcription of ZBTB5. In the absence of p53, ZBTB5 is acetylated at K597 by interacting with p300, and activates transcription of NOXA, which induces apoptosis. In contrast, in the presence of p53, ZBTB5 interacts with p53 and acetylation at ZBTB5 K597 is blocked. ZBTB5 without K597 acetylation interacts with mSin3A/HDAC1 to repress p21/CDKN1A transcription and promote cell proliferation. Cell fate decisions by c-Myc depend on ZBTB5, p53 and p300, and acetylation of ZBTB5 K597.
['Choi|Seo-Hyun|SH|', 'Koh|Dong-In|DI|', 'Ahn|Haemin|H|', 'Kim|Jin Young|JY|', 'Kim|Youngsoo|Y|', 'Hur|Man-Wook|MW|']
D000107:Acetylation D017209:Apoptosis D002460:Cell Line D049109:Cell Proliferation D006801:Humans D051741:Kruppel-Like Transcription Factors D000090063:Proto-Oncogene Mas D019253:Proto-Oncogene Proteins c-bcl-2 D016271:Proto-Oncogene Proteins c-myc D015533:Transcriptional Activation D016159:Tumor Suppressor Protein p53 D050880:p300-CBP Transcription Factors
Cell fate decision c-Myc ZBTB5 p53 Apoptosis NOXA