A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas

Oncogene. 1998 Oct 15;17(15):2013-8. doi: 10.1038/sj.onc.1202122.


SSX genes show extensive nucleotide sequence conservation but little is known of their function. Disruption of SSX1 or SSX2, by chromosome translocation and 'in-frame' fusion to SYT, is a consistent feature of synovial sarcomas. The resulting SYT-SSX1/SSX2 proteins are activators of transcription; transactivation function is located in SYT. Unrearranged SSX1 can repress transcription, and this has been attributed to a putative Krüppel associated box (KRAB) repression domain at the N-terminus. Here we isolated SSX-KRAB domains to specifically measure repression activity, using a previously characterized KOX1-KRAB domain as a control. In our repressor assay SSX1- and SSX2-KRAB domains down-modulated the transactivation of a reporter gene by threefold, compared with 83-fold repression achieved by KOX1-KRAB in the assay. Yeast two-hybrid analysis showed that SSX1-KRAB, unlike KOX1-KRAB, fails to interact with the KRAB co-repressor TIF1beta. These results raise questions about the evolutionary and functional relationship of SSX-KRAB and typical KRAB domains of Krüppel zinc finger genes. We found that full-length SSX1 showed potent (74-fold) repression in our repressor assay, indicating the existence of a repression domain distinct from SSX-KRAB. By assaying deletion constructs of SSX1 we localized repression activity to 33 amino acids at the C-terminus. This novel domain is conserved between SSX family members, and, unlike the KRAB-related domain, is retained on fusion with SYT. This has important implications in understanding the mechanism by which the SYT-SSX fusion protein could contribute to neoplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA-Binding Proteins*
  • Humans
  • Kruppel-Like Transcription Factors
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Repressor Proteins / genetics*
  • Sarcoma / genetics*
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*


  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Neoplasm Proteins
  • Repressor Proteins
  • ZNF10 protein, human
  • synovial sarcoma X breakpoint proteins