SYVN1-mediated ubiquitylation directs localization of MCT4 in the plasma membrane to promote the progression of lung adenocarcinoma.

ABSTRACT: Tumour cells mainly generate energy from glycolysis, which is commonly coupled with lactate production even under normoxic conditions. As a critical lactate transporter, monocarboxylate transporter 4 (MCT4) is highly expressed in glycolytic tissues, such as muscles and tumours. Overexpression of MCT4 is associated with poor prognosis for patients with various tumours. However, how MCT4 function is post-translationally regulated remains largely unknown. Taking advantage of human lung adenocarcinoma (LUAD) cells, this study revealed that MCT4 can be polyubiquitylated in a nonproteolytic manner by SYVN1 E3 ubiquitin ligase. The polyubiquitylation facilitates the localization of MCT4 into the plasma membrane, which improves lactate export by MCT4; in accordance, metabolism characterized by red

SUBMITTER: Zhao M 

PROVIDER: S-EPMC10564934 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature