Regulation of oncogenic Akt ubiquitination and activation by diverse mechanisms in cancer
Description: Narrative The PI3K/Akt signaling is one of most important oncogenic events in human cancers, which regulates many aspects of biological functions including cell proliferation, survival, and metabolism important for cancer initiation and progression. The objectives of this study are to dissect the upstream regulatory mechanisms by which growth factors activate and recruit SETDB1 and E3 ligases TRAF6 to elicit Akt methylation and subsequent K63-linked ubiquitination, to understand how Akt ubiquitination triggers Akt membrane recruitment and activation, and to explore these regulatory mechanisms and its targeting in oncogenic processes. Our study represents a highly innovative and paradigm-shift proposal that will not only open up a new avenue for PI3K/Akt signaling regulation, but also offer new concepts and strategies for cancer targeting.
Funder: National Cancer Institute
Funding type: research
Funder scheme: R01
Start date: 2021-07-12
End date: 2026-06-30
Investigator: HUI-KUAN LIN (lead)
Institution: Duke University
Funded outputs count: 14
Funder award ID: R01CA248037
OpenAlex ID: G9000862192