Structural mechanisms of PTEN regulation

TY - JOUR

T1 - Structural mechanisms of PTEN regulation

AU - Masson, Glenn R.

AU - Williams, Roger L.

N1 - Funding Information: Glenn Masson is supported by an AstraZeneca/ Laboratory of Molecular Biology Blue Skies Fund Grant (BSF33). R.L.W. thanks the MRC and Cancer Research UK for funding (Grants MC_U105184308 and C14801/A21211, respectively). Publisher Copyright: © 2020 Cold Spring Harbor Laboratory Press; all rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/3

Y1 - 2020/3

N2 - The tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) is a tightly regulated enzyme responsible for dephosphorylating the progrowth lipid messenger molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. The carboxy-terminal tail (CTT) of PTEN is key for regulation of the enzyme. When phosphorylated, the unstructured CTT interacts with the phosphatase-C2 superdomain to inactivate the enzyme by preventing membrane association. PTEN mutations associated with cancer also inactivate the enzyme. Alternate translation-initiation sites generate extended isoforms of PTEN, such as PTEN-L that has multiple roles in cells. The extended amino-terminal region bears a signal sequence and a polyarginine sequence to facilitate exit from and entry into cells, respectively, and a membrane-binding helix that activates the enzyme. This amino-terminal region also facilitates mitochondrial and nucleolar localization. This review explores PTEN structure and its impact on localization and regulation.

AB - The tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) is a tightly regulated enzyme responsible for dephosphorylating the progrowth lipid messenger molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. The carboxy-terminal tail (CTT) of PTEN is key for regulation of the enzyme. When phosphorylated, the unstructured CTT interacts with the phosphatase-C2 superdomain to inactivate the enzyme by preventing membrane association. PTEN mutations associated with cancer also inactivate the enzyme. Alternate translation-initiation sites generate extended isoforms of PTEN, such as PTEN-L that has multiple roles in cells. The extended amino-terminal region bears a signal sequence and a polyarginine sequence to facilitate exit from and entry into cells, respectively, and a membrane-binding helix that activates the enzyme. This amino-terminal region also facilitates mitochondrial and nucleolar localization. This review explores PTEN structure and its impact on localization and regulation.

UR - https://www.scopus.com/pages/publications/85081011860

U2 - 10.1101/cshperspect.a036152

DO - 10.1101/cshperspect.a036152

M3 - Article

C2 - 31636093

AN - SCOPUS:85081011860

SN - 2157-1422

VL - 10

JO - Cold Spring Harbor Perspectives in Medicine

JF - Cold Spring Harbor Perspectives in Medicine

IS - 3

M1 - a036152

ER -