BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs.

ABSTRACT: Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich ele

SUBMITTER: Xin W 

PROVIDER: S-EPMC7494854 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature