14-3-3gamma induces oncogenic transformation by stimulating MAP kinase and PI3K signaling.

PloS One
Vijayababu M Radhakrishnan, Jesse D Martinez

Abstract

The 14-3-3 proteins are a set of highly conserved scaffolding proteins that have been implicated in the regulation of a variety of important cellular processes such as the cell cycle, apoptosis and mitogenic signaling. Recent evidence indicates that the expression of some of the family members is elevated in human cancers suggesting that they may play a role in tumorigenesis. In the present study, the oncogenic potential of 14-3-3gamma was shown by focus formation and tumor formation in SCID mice using 14-3-3gamma transfected NIH3T3 mouse fibroblast cells. In contrast, 14-3-3sigma, a putative tumor suppressor, inhibited NIH3T3 transformation by H-ras and c-myc. We also report that activation of both MAP kinase and PI3K signaling pathways are essential for transformation by 14-3-3gamma. In addition, we found that 14-3-3gamma interacts with phosphatidylinositol 3-kinase (PI3K) and TSC2 proteins indicating that it could stimulate PI3K signaling by acting at two points in the signaling pathway. Overall, our studies establish 14-3-3gamma as an oncogene and implicate MAPK and PI3K signaling as important for 14-3-3gamma induced transformation.

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Citations

Aug 27, 2011·BMC Cancer·Vijayababu M RadhakrishnanJesse D Martinez
Oct 13, 2015·Drug Discovery Today·Yasaman Aghazadeh, Vassilios Papadopoulos
Sep 24, 2011·Pathology, Research and Practice·Jianping DengZhenwei Zhao
Dec 3, 2011·Journal of Cellular Biochemistry·Domenic Di Paola, Maria Zannis-Hadjopoulos
Jul 15, 2011·Genes, Chromosomes & Cancer·Vijayababu M RadhakrishnanJesse D Martinez
Nov 11, 2015·Nucleic Acids Research·Pierre-Olivier EstèveSriharsa Pradhan
Nov 12, 2014·International Journal of Oncology·De-Yu ChenWen-Qing Qi
Oct 19, 2017·International Journal of Molecular Sciences·Daniel Brandwein, Zhixiang Wang
Apr 22, 2018·Journal of Cell Science·Katrin RietscherMechthild Hatzfeld
Dec 30, 2017·International Journal of Molecular Medicine·Rui WangZhengxia Wu
Jan 13, 2018·Genes & Cancer·Cecil J GomesJesse D Martinez
Oct 28, 2017·Frontiers in Molecular Neuroscience·Brett Cornell, Kazuhito Toyo-Oka
Jan 8, 2020·International Journal of Molecular Sciences·Abdalla AbdrabouZhixiang Wang
May 30, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Pritsana RaungrutParamee Thongsuksai
Oct 3, 2015·Oncotarget·Jin-Ock KimKwang-Hyun Baek
Sep 5, 2019·Cells·Abdalla AbdrabouZhixiang Wang

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Methods Mentioned

BETA
Transfection
PCR
immunoprecipitations
co-immunoprecipitation
electrophoresis
immunoprecipitation
coimmunoprecipitation

Software Mentioned

Image J

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