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DNAJB1 destabilizes PDCD5 to suppress p53-mediated apoptosis

 Xiandan Cui  ;  Hyo-Kyoung Choi  ;  Young-Seok Choi  ;  Soo-Yeon Park  ;  Gi-Jun Sung  ;  Yoo-Hyun Lee  ;  Jeongmin Lee  ;  Woo Jin Jun  ;  Kyungsup Kim  ;  Kyung-Chul Choi  ;  Ho-Geun Yoon 
 CANCER LETTERS, Vol.357(1) : 307-315, 2015 
Journal Title
Issue Date
Apoptosis/physiology ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism* ; Cell Line, Tumor ; Cell Proliferation/physiology ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; HCT116 Cells ; HEK293 Cells ; HSP40 Heat-Shock Proteins/genetics ; HSP40 Heat-Shock Proteins/metabolism* ; Humans ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism* ; Transfection ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism* ; Ubiquitination
Apoptosis ; DNAJB1 ; PDCD5 ; Ubiquitination ; p53
Although PDCD5 promotes p53-mediated apoptosis in various cancers, little is known about PDCD5 regulation. We recently found that DNAJB1 interacts with PDCD5 and induces the ubiquitin-dependent proteasomal degradation of PDCD5, thereby inhibiting p53-mediated apoptosis. To investigate these novel roles for PDCD5 and DNAJB1, we performed DNAJB1 mapping with PDCD5. PDCD5 specifically binds to the DNAJB1-D5 domain (Δ180-210), which was found to be essential for the stabilization of PDCD5. Further study showed that DNAJB1 post-translationally regulates PDCD5 stability. DNAJB1 ubiquitinated PDCD5 via a ubiquitin-mediated pathway. In human lung A549 cancer cells, DNAJB1 promoted the ubiquitination and degradation of PDCD5 and inhibited p53 activation. However, DNAJB1 knockdown in A549 cells increased the etoposide-induced activation of the p53-mediated apoptosis pathway and repressed cancer cell growth. Because this function was p53 dependent, DNAJB1 depletion increased the expression of p53-targeted apoptosis genes. In conclusion, we screened a novel PDCD5-associating protein, DNAJB1, by yeast two-hybrid screening and provided evidences that DNAJB1 targets PDCD5 to suppress p53-dependent apoptosis of cancer cells. Thus, we identified DNAJB1 as a negative regulator of PDCD5-mediated apoptosis and found that the apoptosis network of PDCD5 regulates cancer cell death.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Cui, Xiandan(최향단)
Choi, Hyo Kyoung(최효경)
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