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TRAF 6 interacts with and ubiquitinates PIK 3 CA to enhance PI 3K activation
Author(s) -
Wang Zixi,
Liu Yuxiang,
Huang Song,
Fang Min
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13080
Subject(s) - ubiquitin ligase , phosphorylation , chemistry , downregulation and upregulation , protein subunit , microbiology and biotechnology , protein kinase b , pi , cell growth , ubiquitin , biology , gene , biochemistry
The PI 3K‐ AKT signaling pathway regulates cell survival, proliferation, and migration. An abnormal activation of PI 3K plays an important role in cancer development. Here, we identify TRAF 6 as a potent E3 ubiquitin ligase for the PI 3K catalytic subunit PIK 3 CA (p110α). TRAF 6 interacts with PIK 3 CA and promotes its nonproteolytic polyubiquitination under serum stimulation. TRAF 6 ubiquitinates both individual and regulatory subunit‐bound PIK 3 CA but does not ubiquitinate the regulatory subunit of PI 3K. The examination of TRAF 6 mRNA expression revealed its upregulation in multiple human malignancies. We demonstrate that overexpression of TRAF 6 greatly enhances PI 3K activation, leading to an increase in AKT phosphorylation and cell growth. We conclude that TRAF 6 is a novel PIK 3 CA regulator whose deregulated overexpression represents a mechanism for PI 3K overactivation in tumors.