SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma
Yuan Shao, Wanli Ren, Hao Dai, Fangli Yang, Xiang Li, Shaoqiang Zhang, Junsong Liu, Xiaobao Yao, Qian Zhao, Xin Sun, Zhiwei Zheng, Chongwen Xu
Abstract
depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.
Topics & Concepts
SKP2AutophagyProtein kinase BUbiquitinCancer researchDegradation (telecommunications)PI3K/AKT/mTOR pathwayThyroid carcinomaChemistryPhosphorylationCell biologyInternal medicineThyroidBiologyMedicineSignal transductionApoptosisUbiquitin ligaseBiochemistryComputer scienceGeneTelecommunicationsUbiquitin and proteasome pathwaysHistone Deacetylase Inhibitors ResearchRNA modifications and cancer