SSBP2 is an in vivo tumor suppressor and regulator of LDB1 stability

Oncogene. 2010 May 27;29(21):3044-53. doi: 10.1038/onc.2010.78. Epub 2010 Mar 29.


SSBP proteins bind and stabilize transcriptional cofactor LIM domain-binding protein1 (LDB1) from proteosomal degradation to promote tissue-specific transcription through an evolutionarily conserved pathway. The human SSBP2 gene was isolated as a candidate tumor suppressor from a critical region of loss in chromosome 5q14.1. By gene targeting, we show increased predisposition to B-cell lymphomas and carcinomas in Ssbp2(-/-) mice. Remarkably, loss of Ssbp2 causes increased LDB1 turnover in the thymus, a pathway exploited in Trp53(-/-)Ssbp2(-/-) mice to develop highly aggressive, immature thymic lymphomas. Using T-cell differentiation as a model, we report a stage-specific upregulation of Ssbp2 expression, which in turn regulates LDB1 turnover under physiological conditions. Furthermore, transcript levels of pTalpha, a target of LDB1-containing complex, and a critical regulator T-cell differentiation are reduced in Ssbp2(-/-) immature thymocytes. Our findings suggest that disruption of the SSBP2-regulated pathways may be an infrequent but critical step in malignant transformation of multiple tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cricetinae
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Lethal
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / pathology
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics


  • DNA-Binding Proteins
  • SSBP2 protein, human
  • Ssbp2 protein, mouse
  • Tumor Suppressor Protein p53