| Abstract |
The murine retrovirus integration site 1 (MRVI1) gene encodes an endoplasmic reticulum (ER)-associated membrane protein involved in calcium signaling, yet its molecular interaction network remains largely undefined. Here, we employed TurboID-based proximity labeling to construct the first comprehensive map of MRVI1-associated proteins in mammalian cells. This analysis identified over 700 candidate interactors, including ER-localized factors and components of intracellular trafficking, consistent with the subcellular localization and signaling 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 signaling-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 labeling, suggesting that MRVI1 may participate in apoptosis-related networks disrupted during oncogenic transformation. Together, our findings demonstrate that MRVI1 forms a functionally diverse protein network that can be selectively remodeled by oncogenic signaling. This study not only uncovers potential mechanisms by which MRVI1 contributes to transformation but also provides a valuable proteomic resource for future investigation of MRVI1 function and regulation.
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