Document Detail


Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition.
MedLine Citation:
PMID:  23045645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 7 (SENP7) variants are naturally expressed in breast epithelia. Breast cancer (BCa) onset down-regulates the short SENP7 splice variant (SENP7S) and enhances the long transcript (SENP7L). Here, we show that SENP7L induction promotes gene expression profiles that favor aberrant proliferation and initiate epithelial-mesenchymal transition (EMT). SENP7L exhibits an interaction domain for the epigenetic remodeler heterochromatin protein 1 α (HP1α) and isopeptidase activity against SUMO-modified HP1α. Loss of this interaction domain, as observed with SENP7S, favors HP1α SUMOylation. SUMOylated HP1α is enriched at E2F-responsive and mesenchymal gene promoters, silences transcription of these genes, and promotes cellular senescence. Elevated SENP7L renders HP1α hypo-SUMOylated, which relieves transcriptional repression of the same genes and concurrently decreases transcription of epithelial-promoting genes via an HP1α-independent mechanism. Consequently, SENP7L levels correlate with EMT, motility, and invasiveness of BCa cells. Stable knockdown of elevated SENP7L levels lessens the dissemination of highly metastatic BCa cells to the lungs from primary implantation sites in in vivo studies. Thus, differential splicing of the SENP7 regulates either tumor suppression or progression.
Authors:
Tasneem Bawa-Khalfe; Long-Sheng Lu; Yong Zuo; Chao Huang; Ruhee Dere; Feng-Ming Lin; Edward T H Yeh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17466-71     Citation Subset:  IM    
Affiliation:
Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. tbawa@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cell Line
Endopeptidases / chemistry,  genetics,  metabolism*,  physiology
Epithelial-Mesenchymal Transition / physiology*
Gene Expression Profiling
Humans
Molecular Sequence Data
RNA, Messenger / genetics
Sequence Homology, Amino Acid
Grant Support
ID/Acronym/Agency:
R01 CA139520/CA/NCI NIH HHS; R01CA239520/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; EC 3.4.-/Endopeptidases; EC 3.4.22.-/SENP7 protein, human
Comments/Corrections

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