Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition

Tasneem Bawa-Khalfe, Long-Sheng Lu, Yong Zuo, Chao Huang, Ruhee Dere, Feng Ming Lin, Edward Yeh

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)17466-17471
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number43
DOIs
Publication statusPublished - Oct 23 2012
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Ubiquitin
Peptide Hydrolases
Breast Neoplasms
Genes
SUMO-1 Protein
Sumoylation
Cell Aging
Transcriptome
Epigenomics
heterochromatin-specific nonhistone chromosomal protein HP-1
Breast
Down-Regulation
Epithelium
Lung
Neoplasms

Keywords

  • Dedifferentiation
  • Epigenetics
  • Posttranslational-modification

ASJC Scopus subject areas

  • General

Cite this

Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition. / Bawa-Khalfe, Tasneem; Lu, Long-Sheng; Zuo, Yong; Huang, Chao; Dere, Ruhee; Lin, Feng Ming; Yeh, Edward.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 43, 23.10.2012, p. 17466-17471.

Research output: Contribution to journalArticle

Bawa-Khalfe, Tasneem ; Lu, Long-Sheng ; Zuo, Yong ; Huang, Chao ; Dere, Ruhee ; Lin, Feng Ming ; Yeh, Edward. / Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 43. pp. 17466-17471.
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