聚(A)聚合酶Star-PAP受稳定相关磷酸肌苷信使调控。

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-06-24 DOI:10.1016/j.jbc.2025.110412

Tianmu Wen, Mo Chen, Vincent L Cryns, Richard A Anderson

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引用次数: 0

摘要

Star-PAP是一种控制基因表达的非规范聚(a)聚合酶。Star-PAP与PIPKI及其产物PI(4,5)P2结合，调节Star-PAP的活性和特定基因的表达。最近的研究揭示了一个核p53-磷酸肌醇信号通路，其中磷脂酰肌醇（PI）转移蛋白（PITPs）和磷酸肌醇激酶/磷酸酶结合p53，依次修饰p53连接的磷酸肌醇并调节p53的功能。在这里，我们证明了多种磷酸肌苷也与Star-PAP偶联以响应应激。该途径由PITP /β与Star-PAP结合启动，并且Star-PAP-磷酸肌肽复合物依次被PI4KII、PIPKI、IPMK和PTEN修饰。Star-PAP-磷酸肌肽复合物的形成增强了小热休克蛋白HSP27和b -晶体蛋白与Star-PAP的结合。敲低PITPs、PIP激酶或HSP27可降低Star-PAP靶点的表达。我们的研究结果表明，PITP /β在Star-PAP-磷酸肌肽复合物的组装中起关键作用，该复合物由PIP激酶/磷酸酶依次相互转化，并将小热休克蛋白招募到这些复合物中，以调节Star-PAP在应激反应中的活性。

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The Poly(A) Polymerase Star-PAP is Regulated by Stably Associated Phosphoinositide Messengers.

Star-PAP is a noncanonical poly(A) polymerase that controls gene expression. Star-PAP was previously reported to bind PIPKI⍺ and its product PI(4,5)P₂, which regulate Star-PAP activity and expression of specific genes. Recent studies have revealed a nuclear p53-phosphoinositide signaling pathway in which the phosphatidylinositol (PI) transfer proteins (PITPs) and phosphoinositide kinases/phosphatases bind p53 to sequentially modify p53-linked phosphoinositides and regulate p53 function. Here we demonstrate that multiple phosphoinositides are also coupled to Star-PAP in response to stress. This pathway is initiated by PITP⍺/β binding to Star-PAP, and the Star-PAP-phosphoinositide complexes are sequentially modified by PI4KII⍺, PIPKI⍺, IPMK, and PTEN. The formation of Star-PAP-phosphoinositide complexes enhances the association of the small heat shock proteins HSP27 and ⍺B-crystallin with Star-PAP. Knockdown of the PITPs, PIP kinases, or HSP27 reduces the expression of Star-PAP targets. Our results demonstrate that PITP⍺/β play a key role in the assembly of Star-PAP-phosphoinositide complexes that are sequentially interconverted by PIP kinases/phosphatases and recruit the small heat shock proteins to these complexes to regulate Star-PAP activity in response to stress.

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来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

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