Title: Identification of PP2A complexes and pathways involved in cell transformation
Authors: Sablina, Anna ×
Hector, Melissa
Colpaert, Nathalie
Hahn, William C #
Issue Date: 15-Dec-2010
Publisher: Waverly Press
Series Title: Cancer Research vol:70 issue:24 pages:10474-10484
Abstract: The simian virus 40 small t (SV40ST) oncoprotein interacts with protein phosphatase 2A (PP2A), an abundantly expressed family of serine-threonine phosphatases. This interaction is essential for the transformation of human cells by SV40, and several PP2A subunits have been implicated as tumor suppressor genes. However, the pathways controlled by specific PP2A complexes involved in cell transformation remain incompletely understood. Using a comprehensive loss-of-function approach, we identified 4 PP2A regulatory subunits [B56α, B56γ, PR72/PR130, and PTPA (protein phosphatase 2A activator)], which when suppressed replaced the expression of SV40ST in human cell transformation. We found that manipulation of complexes containing PP2A B56α, B56γ, and PR72/PR130 activates the pathways regulated by c-Myc, Wnt, and PI3K (phosphoinositide 3-kinase)/Akt in a manner that depends on their specific phosphatase activity. In contrast, suppression of PTPA disrupts the assembly of PP2A heterotrimeric complexes, which leads to the activation of these same oncogenic pathways. These observations delineate the PP2A family members and pathways perturbed by SV40ST during human cell transformation.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Mechanisms of Cell Transformation (VIB-KU Leuven Centre for Cancer Biology)
× corresponding author
# (joint) last author

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