# Discovery of RUVBL1 as a Target of the Marine Alkaloid Caulerpin via MS-Based Functional Proteomics

## TL;DR

This study identifies RUVBL1 as a target of the marine compound caulerpin, suggesting its potential in cancer therapy.

## Contribution

The novel contribution is the discovery of RUVBL1 as a target of caulerpin using MS-based proteomics.

## Key findings

- Caulerpin interacts with RUVBL1, a protein involved in cancer-related processes like chromatin remodeling.
- MS-based methods DARTS and t-LIP-MRM-MS identified RUVBL1 as a key target of caulerpin in cancer cells.
- In silico and biological studies confirmed caulerpin's role in regulating RUVBL1 activity.

## Abstract

Marine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their interaction profiles to identify the macromolecular partners they can modulate. This study focused on the interactome profiling of the marine alkaloid caulerpin (CAU), isolated from the alga Caulerpa cylindracea. Along with the discovery of its antitumor properties, this metabolite has garnered attention for its potential therapeutic applications, including modulation of MAO-B and PPARs involved in inflammatory responses, as well as the discovery of its antitumor properties. Two complementary MS-based proteomic approaches were used to identify CAU target proteins in cancer cells: DARTS, which enabled proteome-wide screening to identify proteins interacting with the compound, and t-LIP-MRM-MS, which pinpointed the target protein regions involved in ligand binding. RUVB-like 1 (RUVBL1), a protein that regulates the essential mechanism of carcinogenesis, including chromatin remodeling, DNA repair, and transcriptional control, was discovered as an intriguing CAU target. These results were corroborated via in silico and biological investigations that elucidated CAU role in the regulation of RUVBL1 activity, highlighting its promising therapeutic relevance.