RNF20 and histone H2B ubiquitylation exert opposing effects in basal-like versus luminal breast cancer.
Granit, Roy Z
Pateras, Ioannis S
Gorgoulis, Vassilis G
AffiliationDepartment of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
MetadataShow full item record
AbstractBreast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors. Consistent with a tumor-suppressive role, silencing of RNF20 in basal-like breast cancer cells increased their proliferation and migration, and their tumorigenicity and metastatic capacity, partly through upregulation of inflammatory cytokines. In contrast, in luminal breast cancer cells, RNF20 silencing reduced proliferation, migration and tumorigenic and metastatic capacity, and compromised estrogen receptor transcriptional activity, indicating a tumor-promoting role. Notably, the effects of USP44 silencing on proliferation and migration in both cancer subtypes were opposite to those of RNF20 silencing. Hence, RNF20 and H2Bub1 have contrasting roles in distinct breast cancer subtypes, through differential regulation of key transcriptional programs underpinning the distinctive traits of each subtype.Cell Death and Differentiation advance online publication, 3 February 2017; doi:10.1038/cdd.2016.126.
CitationRNF20 and histone H2B ubiquitylation exert opposing effects in basal-like versus luminal breast cancer. 2017, Cell Death Differ.
JournalCell Death and Differentiation
- let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery.
- Authors: Spolverini A, Fuchs G, Bublik DR, Oren M
- Issue date: 2017 Oct 19
- The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression.
- Authors: Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, Raver-Shapira N, Minsky N, Pirngruber J, Tarcic G, Hublarova P, Moyal L, Gana-Weisz M, Shiloh Y, Yarden Y, Johnsen SA, Vojtesek B, Berger SL, Oren M
- Issue date: 2008 Oct 1
- Early Loss of Histone H2B Monoubiquitylation Alters Chromatin Accessibility and Activates Key Immune Pathways That Facilitate Progression of Ovarian Cancer.
- Authors: Hooda J, Novak M, Salomon MP, Matsuba C, Ramos RI, MacDuffie E, Song M, Hirsch MS, Lester J, Parkash V, Karlan BY, Oren M, Hoon DS, Drapkin R
- Issue date: 2019 Feb 15
- Histone H2B ubiquitin ligases RNF20 and RNF40 in androgen signaling and prostate cancer cell growth.
- Authors: Jääskeläinen T, Makkonen H, Visakorpi T, Kim J, Roeder RG, Palvimo JJ
- Issue date: 2012 Mar 5
- The RING finger domain E3 ubiquitin ligases BRCA1 and the RNF20/RNF40 complex in global loss of the chromatin mark histone H2B monoubiquitination (H2Bub1) in cell line models and primary high-grade serous ovarian cancer.
- Authors: Dickson KA, Cole AJ, Gill AJ, Clarkson A, Gard GB, Chou A, Kennedy CJ, Henderson BR, Australian Ovarian Cancer Study (AOCS)., Fereday S, Traficante N, Alsop K, Bowtell DD, deFazio A, Clifton-Bligh R, Marsh DJ
- Issue date: 2016 Dec 15