Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Eur J Pharmacol. 2024 Aug 15;977:176753. doi: 10.1016/j.ejphar.2024.176753. Epub 2024 Jun 17.
Phosphoinositide 3-kinase (PI3K) pathway, controlling diverse functions in cells, is one of the most frequently dysregulated pathways in cancer. Several negative regulators have been reported to intricately constrain the overactivation of PI3K pathway. Phosphatidylinoinosidine-3-kinase interacting protein 1 (PIK3IP1), as a unique transmembrane protein, is a newly discovered negative regulator of PI3K pathway. PIK3IP1 negatively regulates PI3K activity by directly binding to the p110 catalytic subunit of PI3K. It has been reported that PIK3IP1 is frequently low expressed in tumors and autoimmune diseases. In tumor cells and impaired cardiomyocyte, PIK3IP1 inhibits cell proliferation and survival. Consistently, the expression of PIK3IP1 is related with the condition of cancer. In addition, PIK3IP1 inhibits the inflammatory response and immune function via maintaining the quiescent state of immune cells. Thus, low expression of PIK3IP1 represents the severe condition of autoimmune diseases. PIK3IP1 is regulated by transcription factors, epigenetic factors or micro-RNAs to facilitate its normal function in different cellular contexts. This review integrates the total findings on PIK3IP1 in different disease, and summaries the structure, biological functions and regulatory mechanisms of PIK3IP1.
磷酸肌醇 3-激酶（PI3K）途径，控制细胞中的多种功能，是癌症中最常失调的途径之一。已经报道了几种负调控因子来精细地限制 PI3K 途径的过度激活。磷脂酰肌醇-3-激酶相互作用蛋白 1（PIK3IP1）作为一种独特的跨膜蛋白，是 PI3K 途径的一种新发现的负调控因子。PIK3IP1 通过直接与 PI3K 的 p110 催化亚基结合，负调控 PI3K 的活性。已经报道 PIK3IP1 在肿瘤和自身免疫性疾病中经常低表达。在肿瘤细胞和受损的心肌细胞中，PIK3IP1 抑制细胞增殖和存活。一致地，PIK3IP1 的表达与癌症的状况有关。此外，PIK3IP1 通过维持免疫细胞的静止状态来抑制炎症反应和免疫功能。因此，PIK3IP1 的低表达代表自身免疫性疾病的严重状况。PIK3IP1 受转录因子、表观遗传因子或 micro-RNAs 的调节，以促进其在不同细胞环境中的正常功能。本综述综合了 PIK3IP1 在不同疾病中的研究结果，总结了 PIK3IP1 的结构、生物学功能和调节机制。
