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 - http://www.scopus.com/inward/record.url?scp=85081011860&partnerID=8YFLogxK
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 -