CKAP4 in hepatocellular carcinoma: competitive RETREG1/FAM134B binding, reticulophagy regulation, and cancer progression.

ABSTRACT: RETREG1/FAM134B is known for its role as a reticulophagy receptor. Our previous study established that RETREG1 is upregulated in hepatocellular carcinoma (HCC) and contributes to disease progression by activating the AKT signaling pathway. However, the specific mechanisms underlying the elevated expression of RETREG1 in HCC remain unclear. This study unveils the interaction of RETREG1 with CKAP4 and TRIM21. We demonstrated that TRIM21 ubiquitinates RETREG1 at K247 and K252, facilitating its proteasomal degradation. Conversely, CKAP4 shields RETREG1 from degradation by competitively binding to it, revealing a novel post-translational modification mechanism for RETREG1. By modulating RETREG1 expression, CKAP4, and TRIM21 intricately regulate reticulophagy. Additionally, we observed that stre

SUBMITTER: Mo J 

PROVIDER: S-EPMC11925109 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature