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YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

Authors
 Soo-Yeon Park  ;  Hyo-Kyoung Choi  ;  Seong-Ho Jo  ;  JaeSung Seo  ;  Eun-Jeong Han  ;  Kyung-Chul Choi  ;  Jae-Wook Jeong  ;  Youngsok Choi  ;  Ho-Geun Yoon 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol.1853(5) : 1060-1072, 2015 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 
ISSN
 0167-4889 
Issue Date
2015
MeSH
Animals ; Apoptosis Regulatory Proteins/metabolism* ; Cell Line, Tumor ; DNA Damage* ; Humans ; Leupeptins/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Models, Biological ; Muscle Proteins/metabolism* ; Neoplasm Proteins/metabolism* ; Protein Binding ; Protein Multimerization ; Protein Stability/drug effects ; Repressor Proteins/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Ubiquitination
Keywords
Apoptosis ; Genotoxic stress ; PDCD5 ; TP53 ; YAF2
Abstract
Programmed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses.
Full Text
http://www.sciencedirect.com/science/article/pii/S0167488915000154
DOI
10.1016/j.bbamcr.2015.01.006
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Seo, Jae Sung(서재성)
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Jo, Seong Ho(조성호)
Choi, Hyo Kyoung(최효경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139470
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