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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-12, Vol.533 (4), p.1247-1254
Main Authors: Choi, Seo-Hyun, Koh, Dong-In, Ahn, Haemin, Kim, Jin Young, Kim, Youngsoo, Hur, Man-Wook
Format: Article
Language:English
Subjects:
Acetylation
Apoptosis
c-Myc
Cell fate decision
Cell Line
Cell Proliferation
Humans
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
NOXA
p300-CBP Transcription Factors - metabolism
p53
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-myc - metabolism
Transcriptional Activation
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - physiology
ZBTB5
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Summary: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. •ZBTB5 is a direct transcriptional target of the c-Myc.•In the absence of p53, ZBTB5 is acetylated at K597 and activates transcription of the NOXA, which induces apoptosis.•In the presence of p53, ZBTB5 acetylation at the K597 is blocked, which promotes cell proliferation.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.09.137