The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Academic Article uri icon

Overview

abstract

  • Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

publication date

  • March 1, 2018

Research

keywords

  • F-Box Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • Neoplasm Proteins
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Sarcoma, Synovial

Identity

PubMed Central ID

  • PMC5881394

Scopus Document Identifier

  • 85042819346

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.01.018

PubMed ID

  • 29502955

Additional Document Info

volume

  • 33

issue

  • 3