TY - JOUR
T1 - Phosphatase
T2 - PP2A structural importance, regulation and its aberrant expression in cancer
AU - Seshacharyulu, Parthasarathy
AU - Pandey, Poomy
AU - Datta, Kaustubh
AU - Batra, Surinder K.
N1 - Funding Information:
The authors on this work are supported, in part, by Grants from the Department of Defense ( PC074289 ) and the National Institutes of Health ( R01 CA 138791 , RO1 CA 140432).
PY - 2013/7/10
Y1 - 2013/7/10
N2 - Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase and regulates the function by dephosphorylating many critical cellular molecules like Akt, p53, c-Myc and β-catenin. It plays a critical role in cellular processes, such as cell proliferation, signal transduction and apoptosis. Structurally, it is multifarious as it is composed of catalytic, scaffold and regulatory subunits. The catalytic and scaffold subunits have two isoforms and the regulatory subunit has four different families containing different isoforms. The regulatory subunit is the most diverse with temporal and spatial specificity. PP2A undergoes post-translational modifications (i.e. phosphorylation and methylation), which in turn, regulates its enzymatic activity. Aberrant expression, mutations and somatic alterations of the PP2A scaffold and regulatory subunits have been observed in various human malignancies, including lung, breast, skin and colon cancer, highlighting its role as a 'tumor suppressor'. This review is focused on the structural complexity of serine/threonine phosphatase PP2A and summarizes its expression pattern in cancer. Additionally, the PP2A interacting and regulatory proteins and substrates are also discussed. Finally, the mouse models developed to understand the biological role of PP2A subunits in an in vivo model system are also reviewed in this article.
AB - Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase and regulates the function by dephosphorylating many critical cellular molecules like Akt, p53, c-Myc and β-catenin. It plays a critical role in cellular processes, such as cell proliferation, signal transduction and apoptosis. Structurally, it is multifarious as it is composed of catalytic, scaffold and regulatory subunits. The catalytic and scaffold subunits have two isoforms and the regulatory subunit has four different families containing different isoforms. The regulatory subunit is the most diverse with temporal and spatial specificity. PP2A undergoes post-translational modifications (i.e. phosphorylation and methylation), which in turn, regulates its enzymatic activity. Aberrant expression, mutations and somatic alterations of the PP2A scaffold and regulatory subunits have been observed in various human malignancies, including lung, breast, skin and colon cancer, highlighting its role as a 'tumor suppressor'. This review is focused on the structural complexity of serine/threonine phosphatase PP2A and summarizes its expression pattern in cancer. Additionally, the PP2A interacting and regulatory proteins and substrates are also discussed. Finally, the mouse models developed to understand the biological role of PP2A subunits in an in vivo model system are also reviewed in this article.
KW - Dephosphorylation
KW - Holoenzyme
KW - PP2A subunits
KW - Phosphorylation
KW - Protein phosphatase type 2A (PP2A)
KW - Signaling
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U2 - 10.1016/j.canlet.2013.02.036
DO - 10.1016/j.canlet.2013.02.036
M3 - Review article
C2 - 23454242
AN - SCOPUS:84878431342
VL - 335
SP - 9
EP - 18
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -