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

Wang Y, Klumpp S, Amin HM, Liang H, Li J, Estrov Z, Zweidler-McKay P, Brandt SJ, Agulnick A, Nagarajan L
Oncogene. 2010 29 (21): 3044-53

PMID: 20348955 · PMCID: PMC2878399 · DOI:10.1038/onc.2010.78

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.

MeSH Terms (14)

Animals Cell Differentiation Cricetinae DNA-Binding Proteins Genes, Lethal Genes, Tumor Suppressor Humans Mice Mice, Inbred C57BL Mice, Knockout T-Lymphocytes Thymus Gland Transcription, Genetic Tumor Suppressor Protein p53

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