TSPYL5 suppresses p53 levels and function by physical interaction with USP7 (Nat Cell Biol, 2011, 13:102-108)

報告日期: 2011/03/11
報告時間: 17:10/18:00
報告學生: 徐依鈴 (英文報告)
講評老師: 賴明德

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0311-2.pdf

TSPYL5 suppresses p53 levels and function by physical interaction with USP7
Mirjam T. Epping, Lars A.T. Meijer, Oscar Krijgsman, Johannes L. Bos, Pier Paolo Pandolfi and René Bernard
Nature Cell Biology, 2011, 13:102-108
Speaker: 徐依鈴
Time: 2011/3/11 17:00-17:50
Place: Room 602
Background:Previously, authors have reported a prognostic gene signature which can predict the clinical outcome of breast cancers patients. This gene signature comprises 70 genes involved in many signaling pathways, such as cell cycle, invasion, metastasis and angiogenesis. Among these genes, TSPYL5 (TSPY-like 5) is a gene of unknown function. TSPYL5 is located on chromosome 8q22 that is frequently amplified in breast cancer, which suggests that TSPYL5 has a causal role in breast cancer oncogenesis.
Objective:To study the role of TSPYL5 in breast cancer, first, authors investigated whether TSPYL5 is an independent marker of breast cancer by analyzing microarray gene expression data of 295 breast cancer patients. Second, to gain insight into TSPYL5 function, they searched for proteins that interact with TSPYL5 by using pull-down assay and LC–MS/MS (liquid chromatography mass spectrometry/mass spectrometry) analysis.
Results:They found that high TSPYL5 expression has poor outcome in breast cancer. LC-MS/MS analysis identified that USP7 (ubiquitin-specific protease 7) was TSPYL5-associated protein. USP7 has been known as a deubiquitylase for the p53 tumor suppressor. Authors demonstrated that TSPYL5 reduced USP7 enzyme activity towards p53, resulting in increased p53 ubiquitylation, reduced p53 protein levels and p53-target genes expressions. In addition, TSPYL5 prevented cells from p53-dependent cell proliferation arrest and oncogene-induced senescence, as well as contributed to oncogenic transformation and clonogenic ability.
Conclusion:In this study, authors demonstrate that TSPYL5 is an independent marker of poor outcome in breast cancer, and TSPYL5 suppresses p53 protein level through its physical interaction with USP7, resulting in inhibitions of p53 transactivation and target gene transcription.
References: van ‘t Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002).