Approaches to Investigating the Protein Interactome of PTEN,Journal of Proteome Research

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Approaches to Investigating the Protein Interactome of PTEN
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-10-19 , DOI: 10.1021/acs.jproteome.0c00570
Sarah L Smith ₁ , Andrew R Pitt _{1,

2} , Corinne M Spickett ₁

Affiliation

The tumor suppressor phosphatase and tensin homologue (PTEN) is a redox-sensitive dual specificity phosphatase with an essential role in the negative regulation of the PI3K-AKT signaling pathway, affecting metabolic and cell survival processes. PTEN is commonly mutated in cancer, and dysregulation in the metabolism of PIP₃ is implicated in other diseases such as diabetes. PTEN interactors are responsible for some functional roles of PTEN beyond the negative regulation of the PI3K pathway and are thus of great importance in cell biology. Both high-data content proteomics-based approaches and low-data content PPI approaches have been used to investigate the interactome of PTEN and elucidate further functions of PTEN. While low-data content approaches rely on co-immunoprecipitation and Western blotting, and as such require previously generated hypotheses, high-data content approaches such as affinity pull-down proteomic assays or the yeast 2-hybrid system are hypothesis generating. This review provides an overview of the PTEN interactome, including redox effects, and critically appraises the methods and results of high-data content investigations into the global interactome of PTEN. The biological significance of findings from recent studies is discussed and illustrates the breadth of cellular functions of PTEN that can be discovered by these approaches.

中文翻译：

研究PTEN蛋白相互作用组的方法

肿瘤抑制磷酸酶和张力蛋白同源物（PTEN）是氧化还原敏感的双特异性磷酸酶，在PI3K-AKT信号传导途径的负调控中起重要作用，影响代谢和细胞存活过程。PTEN通常在癌症中发生突变，并且在PIP ₃的代谢中失调与其他疾病有关，例如糖尿病。除了PI3K途径的负调控外，PTEN相互作用体还负责PTEN的某些功能性作用，因此在细胞生物学中非常重要。基于高数据含量蛋白质组学的方法和低数据含量PPI方法均已用于研究PTEN的相互作用组并阐明PTEN的进一步功能。低数据含量的方法依赖于共免疫沉淀和蛋白质印迹，因此需要先前生成的假设，而高数据含量的方法（如亲和力下拉蛋白质组学测定法或酵母2杂交系统）则是产生假说的。这篇综述概述了PTEN相互作用基因组，包括氧化还原作用，并严格评估PTEN全球相互作用组的高数据含量调查的方法和结果。讨论了最近研究发现的生物学意义，并阐明了可通过这些方法发现的PTEN细胞功能的广度。

更新日期：2020-10-19

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