Phosphorylation by IKKβ Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer
Chenxi Zhong, Guosheng Xiong, Haitang Yang, Xiaohua Du, Jiankui Du, Feng Yao, Wentao Fang, Yuezhen Deng
Abstract
) mice. Mechanistically, tumor necrosis factor α (TNFα) treatment decreased the HMGCL protein level, and IKKβ interacted with HMGCL and phosphorylated it at Ser258, which destabilized HMGCL. Moreover, NEDD4 was identified as the E3 ligase for HMGCL and promoted its degradation. In addition, mutation of Ser258 to alanine inhibited the ubiquitination of HMGCL by NEDD4 and thus inhibited the anchorage-independent growth of lung cancer cells more efficiently than did wild-type HMGCL. In summary, this study demonstrated a link between TNFα-mediated inflammation and cancer metabolism.
Topics & Concepts
Ubiquitin ligaseCarcinogenesisLung cancerCancerInflammationTumor necrosis factor alphaUbiquitinCancer researchCancer cellDownregulation and upregulationBiologyPhosphorylationChemistryBiochemistryEndocrinologyInternal medicineImmunologyMedicineGeneticsGeneCancer, Hypoxia, and MetabolismCancer-related molecular mechanisms researchUbiquitin and proteasome pathways