PIK3IP1: structure, aberration, function, and regulation in diseases
Yingjie Jia1, Pengxing He1, Xubin Ma1
1Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Abstract:
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.
Insights
Phosphatidylinositol-3-kinase interacting protein 1 (PIK3IP1) is a novel negative regulator of the PI3K pathway. Low PIK3IP1 expression correlates with cancer and autoimmune diseases, impacting cell proliferation, survival, and immune function.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The Phosphoinositide 3-kinase (PI3K) pathway is crucial for cellular functions and frequently dysregulated in cancer.
- Negative regulators are essential for controlling PI3K pathway overactivation.
- Phosphatidylinositol-3-kinase interacting protein 1 (PIK3IP1) is a newly identified transmembrane protein that negatively regulates PI3K activity.
Purpose of the Study:
- To review the structure, biological functions, and regulatory mechanisms of PIK3IP1.
- To integrate findings on PIK3IP1 in various diseases, particularly cancer and autoimmune disorders.
- To highlight the role of PIK3IP1 as a negative regulator of the PI3K pathway.
Main Methods:
- Literature review integrating existing research findings.
- Analysis of PIK3IP1's interaction with the p110 catalytic subunit of PI3K.
- Examination of PIK3IP1 expression patterns in different disease contexts.
Main Results:
- PIK3IP1 directly binds to the p110 catalytic subunit, inhibiting PI3K activity.
- Low PIK3IP1 expression is frequently observed in tumors and autoimmune diseases.
- PIK3IP1 inhibits tumor cell proliferation and survival, and maintains immune cell quiescence.
Conclusions:
- PIK3IP1 plays a critical role in suppressing PI3K pathway overactivation.
- Dysregulation of PIK3IP1 is linked to the pathogenesis of cancer and autoimmune diseases.
- Understanding PIK3IP1's regulatory mechanisms is vital for therapeutic strategies in these conditions.
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