SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.

ABSTRACT: Lymph node (LN) metastasis is the dominant cause of death in bladder cancer (BCa) patients, but the underlying mechanism remains largely unknown. In recent years, accumulating studies have confirmed that bidirectional mitochondria-nucleus communication is essential for sustaining multiple function of mitochondria. However, little has been studied regarding whether and how the translocation of mitochondrial proteins is involved in LN metastasis. In this study, we first identified that the SUMO E3 ligase MUL1 was significantly downregulated in LN-metastatic BCa tissues and correlated with a good prognosis. Mechanistically, MUL1 SUMOylated HSPA9 at the K612 residue, leading to HSPA9 export from mitochondria and interaction with SUZ12 and in the nucleus. Consequently, MUL1 induced the ubiquiti

SUBMITTER: Wu J 

PROVIDER: S-EPMC11302872 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature