Abstract
LSD1 is a critical chromatin modulator that controls cellular pluripotency and differentiation through the demethylation of H3K4me1/2. Overexpression of LSD1 has been observed in many types of tumors and is correlated with its oncogenic effects in tumorigenesis. However, the mechanism leading to LSD1 upregulation in tumors remains unclear. Using an unbiased siRNA screening against all the human deubiquitinases, we identified USP28 as a bona fide deubiquitinase of LSD1. USP28 interacted with and stabilized LSD1 via deubiquitination. USP28 overexpression correlated with LSD1 upregulation in multiple cancer cell lines and breast tumor samples. Knockdown of USP28 resulted in LSD1 destabilization, leading to the suppression of cancer stem cell (CSC)-like characteristics invitro and inhibition of tumorigenicity invivo, which can be rescued by ectopic LSD1 expression. Our study reveals a critical mechanism underlying the epigenetic regulation by USP28 and provides another treatment approach against breast cancer
| Original language | English |
|---|---|
| Pages (from-to) | 224-236 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 17 2013 |
Bibliographical note
Funding Information:We thank Cathy Anthony for critical reading and editing of this manuscript. This work was supported by grants from NIH (2 RO1CA125454), Susan G. Komen Foundation (KG081310), Mary Kay Ash Foundation (to B.P.Z.), and American Cancer Society Research Scholar Award (RSG13187-01 to Y.W.).
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
