Pathologic significance of SET/I2PP2A-mediated PP2A and non-PP2A pathways in polycystic ovary syndrome (PCOS)

SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal sy...

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Bibliographic Details
Published in:Clinica chimica acta 2017-01, Vol.464, p.155-159
Main Authors: Jiang, Shi-Wen, Xu, Siliang, Chen, Haibin, Liu, Xiaoqiang, Tang, Zuoqing, Cui, Yugui, Liu, Jiayin
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Androgen
Animals
Anti-SET
Female
Histone Chaperones - metabolism
Humans
Hyperandrogenism
Molecular Targeted Therapy
Oocytes - metabolism
PCOS
Polycystic Ovary Syndrome - drug therapy
Polycystic Ovary Syndrome - metabolism
Polycystic Ovary Syndrome - pathology
PP2A
Protein Phosphatase 2 - metabolism
SET
Transcription Factors - metabolism
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Summary:SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed. •SET is involved in DNA replication, histone modification, nucleosome assembly, and transcriptional control.•SET is overexpressed in ovaries of PCOS patients, modulates P450c17, and contributes to hyperandrogenism.•SET may bind to human P450c17 promoter and regulate P450c17 expression in human theca cells.•SET could be a therapeutic target, and anti-SET drugs such as ceramide could be useful for treating PCOS.
ISSN:0009-8981
1873-3492
DOI:10.1016/j.cca.2016.11.010