SUMOylation modulates the stability and function of PI3K-p110β - Archive ouverte HAL Access content directly
Journal Articles Cellular and Molecular Life Sciences Year : 2021

SUMOylation modulates the stability and function of PI3K-p110β

Abstract

Class I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers. Here we sought to evaluate the putative regulation of p110β by SUMO. Our data show that p110β can be modified by SUMO1 and SUMO2 in vitro, in transfected cells and under completely endogenous conditions, supporting the physiological relevance of p110β SUMOylation. We identify lysine residue 952, located at the activation loop of p110β, as essential for SUMOylation. SUMOylation of p110β stabilizes the protein increasing its activation of AKT which promotes cell growth and oncogenic transformation. Finally, we show that the regulatory subunit p85β counteracts the conjugation of SUMO to p110β. In summary, our data reveal that SUMO is a novel p110β interacting partner with a positive effect on the activation of the PI3K pathway.
Fichier principal
Vignette du fichier
CMLS2021pp4043-4065.pdf (5.16 Mo) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-03203257 , version 1 (11-10-2021)

Identifiers

Cite

Ahmed El Motiam, Carlos de La Cruz-Herrera, Santiago Vidal, Rocío Seoane, Maite Baz-Martínez, et al.. SUMOylation modulates the stability and function of PI3K-p110β. Cellular and Molecular Life Sciences, 2021, 78, pp.4053-4065. ⟨10.1007/s00018-021-03826-6⟩. ⟨hal-03203257⟩
42 View
67 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More