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Post-Translational Modifications of PTEN and their Potential Therapeutic Implications

[ Vol. 11 , Issue. 5 ]

Author(s):

G. Singh and A. M. ChanPages 536-547 (12)

Abstract:


PTEN is a tumor suppressor gene localized to human chromosome 10q23.31, a genomic region frequently lost in glioblastoma and prostate cancer. The fact that PTEN encodes a lipid phosphatase with specificity towards phosphatidylinositol-3,4,5-triphosphate renders it a gate-keeper of the phosphatidylinositol 3-kinase pathway. Numerous physiological processes have been ascribed to this evolutionarily conserved molecule including proliferation, cell size determination, survival, differentiation, and cell fate specification. Indeed, mutation in PTEN gene is the genetic cause of Cowden Syndrome. Structurally, the 54-kilodalton protein is composed of two major functional domains crucial for catalytic and membrane binding functions. Additional regulatory regions in both amino- and carboxyl-termini further dictate its structural integrity, catalytic activity, and subcellular localization. Extensive characterization of PTEN primary coding sequence has revealed a multitude of post-translational modifications that fine-tune its biochemical properties. These include phosphorylation, ubiquitination, redox modifications, and acetylation. This article aims to provide an indepth review of the diverse post-translational modifications of PTEN, focusing on their biological relevance in both normal and cancer cells. The potential applications to cancer therapy by modulating the post-translational modifications of PTEN will also be discussed.

Keywords:

PTEN, phosphatase, tumor suppressor, post-translational, phosphorylation, ubiquitination, redox, acetylation, Acute Myeloid Leukemia, Epidermal Growth Factor Receptor, Glutathione-S-Transferase, Histone acetyltransferase, Promyelocytic Leukemia Protein, Reactive Oxygen Species, Histone deacetylase

Affiliation:

Department of Pediatrics, Division of Hematology/Oncology/BMT, Medical College of Wisconsin,8701 Watertown Plank Road, Milwaukee, WI 53226, USA.



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