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Zbtb7c is a molecular 'off' and 'on' switch of Mmp gene transcription

Authors
 Bu-Nam Jeon  ;  Jae-Hyeon Yoon  ;  Min-Kyeong Kim  ;  Won-Il Choi  ;  Dong-In Koh  ;  Benjamin Hur  ;  Kunhong Kim  ;  Kyung-Sup Kim  ;  Man-Wook Hur 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, Vol.1859(11) : 1429-1439, 2016 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 
ISSN
 1874-9399 
Issue Date
2016
MeSH
Amino Acid Sequence ; Animals ; Humans ; Matrix Metalloproteinases/genetics* ; Mice ; NIH 3T3 Cells ; Promoter Regions, Genetic ; Proteins/chemistry ; Proteins/genetics* ; Proteolysis ; Sequence Homology, Amino Acid ; Transcription, Genetic* ; Tumor Necrosis Factor-alpha/administration & dosage ; Ubiquitination
Keywords
Mmps ; NCoR ; Zbtb7c (Kr-pok) ; c-Jun ; p-Jnk
Abstract
Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that play roles in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. The expression of MMP gene is tightly regulated and shows cell- and tissue-specific expression patterns. Despite their differential expression, MMP genes have AP-1 (activator protein-1) binding elements within their promoters. Interestingly, c-JUN phosphorylation by cytokine signaling decreased its interaction with NCoR, but increased its interaction with p300, resulting in activation of MMP gene transcription. Here, we found that Zbtb7c (Kr-pok) is a critical component of a transcriptional repressor complex containing c-Jun and NCoR. c-Jun, bound at AP-1, interacts with Zbtb7c, which in turn recruits an NCoR/Hdac3 complex to repress several Mmp (-8, -10, -13, and -16) genes. The molecular interaction between c-Jun and Zbtb7c also prevents phosphorylation of c-Jun by p-Jnk, However, Zbtb7c phosphorylation by p-Jnk (induced by TNFα), and its (Zbtb7c) subsequent degradation by the ubiquitin-mediated proteasomal pathway, leads to c-Jun phosphorylation by p-Jnk. Promoter-bound p-c-Jun then recruits the coactivator p300 to upregulate Mmp gene. Overall, these findings show that Zbtb7c is a key molecule that recruits an NCoR/Hdac3 complex to inhibit phosphorylation of c-Jun, and thereby repress Mmp gene expression.
Full Text
http://www.sciencedirect.com/science/article/pii/S1874939916301894
DOI
10.1016/j.bbagrm.2016.09.004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Dong In(고동인)
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Jeon, Bu Nam(전부남)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152232
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