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SSBP2 是一种体内肿瘤抑制因子，可调节 LDB1 的稳定性。

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

机构信息

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

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

DOI:10.1038/onc.2010.78
PMID:20348955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2878399/
Abstract

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.

摘要

SSBP 蛋白通过一种进化上保守的途径与 LIM 结构域结合蛋白 1（LDB1）结合并稳定其免于蛋白酶体降解，从而促进组织特异性转录。人类 SSBP2 基因作为染色体 5q14.1 缺失区域的候选肿瘤抑制基因被分离出来。通过基因靶向，我们发现 Ssbp2(-/-) 小鼠更容易发生 B 细胞淋巴瘤和癌。值得注意的是，Ssbp2 的缺失导致胸腺中 LDB1 周转率增加，Trp53(-/-)Ssbp2(-/-) 小鼠利用该途径发展出高度侵袭性的未成熟胸腺淋巴瘤。我们使用 T 细胞分化作为模型，报告了 Ssbp2 表达的特定阶段上调，这反过来又在生理条件下调节 LDB1 的周转率。此外，LDB1 包含的复合物的靶标 pTalpha 的转录本水平和 T 细胞分化的关键调节剂在 Ssbp2(-/-)未成熟胸腺细胞中降低。我们的发现表明，破坏 SSBP2 调节的途径可能是多种组织恶性转化中罕见但关键的步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/4e77d74ce2f1/nihms177312f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/bf9a3770b6f5/nihms177312f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/35dc6b0500e2/nihms177312f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/b6f984032859/nihms177312f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/c8227e18d5a4/nihms177312f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/0365296b5c41/nihms177312f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/4e77d74ce2f1/nihms177312f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/bf9a3770b6f5/nihms177312f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/35dc6b0500e2/nihms177312f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/b6f984032859/nihms177312f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/c8227e18d5a4/nihms177312f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/0365296b5c41/nihms177312f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec03/2878399/4e77d74ce2f1/nihms177312f6.jpg

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