Identification of MRVI1-interacting proteins by biotin-based proximity labelling reveals NPM–ALK-dependent interaction dynamics

作者：Kosuke Higashi, Y. Tanaka, Hidetaka Kosako, Kazumasa Aoyama · 发表于：The Journal of Biochemistry · 年份：2025 · DOI：10.1093/jb/mvaf057 · 被引用次数：1 · 研究领域：Biotin and Related Studies、Neuroblastoma Research and Treatments、Monoclonal and Polyclonal Antibodies Research

The murine retrovirus integration site 1 (MRVI1) gene encodes an endoplasmic reticulum (ER)-associated membrane protein involved in calcium signalling, yet its molecular interaction network remains largely undefined. Here, we employed TurboID-based proximity labelling to construct the first comprehensive map of MRVI1-associated proteins in mammalian cells. This analysis identified >700 candidate interactors, including ER-localized factors and components of intracellular trafficking, consistent with the subcellular localization and signalling role of MRVI1. To investigate oncogenic modulation, we examined how co-expression of NPM-ALK-a constitutively active tyrosine kinase implicated in lymphoid malignancies-reshapes the MRVI1 interactome. Quantitative proteomics revealed that while the overall composition of MRVI1-associated proteins was largely preserved, a subset of interactions was selectively enhanced or attenuated by NPM-ALK. The association of MRVI1 with several signalling-related proteins was enhanced by NPM-ALK, including 12 proteins that have all been previously implicated in cancer-related pathways. In contrast, proteins whose interaction with MRVI1 was suppressed were functionally enriched in the Gene Ontology term 'negative regulation of apoptotic process'. Notably, anti-apoptotic regulators such as DDB1, PHB2 and NOTCH2 showed significantly reduced proximity labelling, suggesting that MRVI1 may participate in apoptosis-related networks disrupted during oncogenic ...