7 252

Cited 0 times in

Ubiquitin ligase CHIP induces TRAF2 proteasomal degradation and NF-κB inactivation to regulate breast cancer cell invasion.

 Kang Won Jang  ;  Kyung Hye Lee  ;  Ji Hyung Chung  ;  Ye Sun Han  ;  Eunsuk Kim  ;  Hyun Ju Jeon  ;  Eun Young Choi  ;  Taewon Jin  ;  Soo Hyuk Kim 
 Journal of Cellular Biochemistry, Vol.112(12) : 3612-3620, 2011 
Journal Title
 Journal of Cellular Biochemistry 
Issue Date
Transcriptional factor nuclear factor-kappaB (NF-κB) plays a crucial role in human breast cancer cell invasion and metastasis. The carboxyl terminus of Hsc70-interacting protein (CHIP) is a U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins. In this study, we investigated the role of CHIP in the NF-κB pathway in the invasion of MDA-MB-231 cells, a highly aggressive breast cancer cell line. We showed that overexpression of CHIP significantly inhibits the invasion of the MDA-MB-231 cells. The overexpression of CHIP suppressed expression of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 cells. Moreover, CHIP strongly inhibited the nuclear localization and the transcriptional activity of NF-κB. The activation of the IkappaB kinase complex (IKK) was also blocked by CHIP overexpression. Importantly, CHIP overexpression resulted in a significant decrease in the level of TNF receptor-associated factor 2 (TRAF2), an upstream key player in the NF-κB pathway. However, the level of TRAF2 was restored after treatment with a proteasome inhibitor, MG-132. Moreover, CHIP overexpression promoted the ubiquitination of TRAF2. We also found cell invasion significantly decreased in cells transfected with TRAF2 small interfering RNA (siRNA). In contrast, when CHIP expression was suppressed by siRNA in poorly invasive MCF-7 cells, cell invasion significantly increased in conjunction with enhanced NF-κB activation and TRAF2 levels. Taken together, these results suggest that CHIP regulates NF-κB-mediated cell invasion via the down-regulation of TRAF2.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
Yonsei Authors
김수혁(Kim, Soo Hyuk) ; 김은숙(Kim, Eun Suk) ; 장강원(Jang, Kang Won) ; 전현주(Jeon, Hyun Ju) ; 정지형(Chung, Ji Hyung) ; 진태원(Jin, Tae Won) ; 최은영(Choi, Eun Young)
사서에게 알리기
Full Text
RIS (EndNote)
XLS (Excel)


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.