PMID- 21793045
OWN - NLM
STAT- MEDLINE
DCOM- 20120406
LR  - 20220408
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 112
IP  - 12
DP  - 2011 Dec
TI  - Ubiquitin ligase CHIP induces TRAF2 proteasomal degradation and NF-kappaB 
      inactivation to regulate breast cancer cell invasion.
PG  - 3612-20
LID - 10.1002/jcb.23292 [doi]
AB  - Transcriptional factor nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB. 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-kappaB 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-kappaB activation and TRAF2 levels. Taken together, 
      these results suggest that CHIP regulates NF-kappaB-mediated cell invasion via the 
      down-regulation of TRAF2.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Jang, Kang Won
AU  - Jang KW
AD  - Graduate Program in Science for Aging & Yonsei Research Institute of Aging 
      Science, Yonsei University, Seoul 120-749, Korea.
FAU - Lee, Kyung Hye
AU  - Lee KH
FAU - Kim, Soo Hyuk
AU  - Kim SH
FAU - Jin, Taewon
AU  - Jin T
FAU - Choi, Eun Young
AU  - Choi EY
FAU - Jeon, Hyun Ju
AU  - Jeon HJ
FAU - Kim, Eunsuk
AU  - Kim E
FAU - Han, Ye Sun
AU  - Han YS
FAU - Chung, Ji Hyung
AU  - Chung JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA Primers)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - EC 2.3.2.27 (STUB1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Base Sequence
MH  - Breast Neoplasms/enzymology/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - DNA Primers
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - Humans
MH  - NF-kappa B/*metabolism
MH  - *Neoplasm Invasiveness
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Proteolysis
MH  - Real-Time Polymerase Chain Reaction
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
EDAT- 2011/07/28 06:00
MHDA- 2012/04/07 06:00
CRDT- 2011/07/28 06:00
PHST- 2011/07/28 06:00 [entrez]
PHST- 2011/07/28 06:00 [pubmed]
PHST- 2012/04/07 06:00 [medline]
AID - 10.1002/jcb.23292 [doi]
PST - ppublish
SO  - J Cell Biochem. 2011 Dec;112(12):3612-20. doi: 10.1002/jcb.23292.