Yuxia Hu, Zhao Zhang, Qiyu Mao, Xiang Zhang, Aihua Hao, Yu Xun, Yeda Wang, Lin Han, Wuqiang Zhan, Qianying Liu, Yue Yin, Chao Peng, Eva Marie Y Moresco, Zhenguo Chen, Bruce Beutler, Lei Sun
Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability...
February 8, 2024: Nature Structural & Molecular Biology