# Met1-linked ubiquitination in cell signaling regulation

## TL;DR

This paper reviews how Met1-linked ubiquitination regulates cell signaling and its role in various biological processes.

## Contribution

The paper provides a comprehensive review of recent advances in Met1-linked ubiquitination's signaling mechanisms.

## Key findings

- Met1-Ub is generated by LUBAC and activates NF-κB signaling through NEMO modification.
- Met1-Ub is involved in multiple pathways like MAPK, Wnt/β-Catenin, and interferon signaling.
- Met1-Ub influences processes such as angiogenesis, protein quality control, and autophagy.

## Abstract

Met1-linked ubiquitination (Met1-Ub), also known as linear ubiquitination, is a newly identified atypical type of polyubiquitination that is assembled via the N-terminal methionine (Met1) rather than an internal lysine (Lys) residue of ubiquitin. The linear ubiquitin chain assembly complex (LUBAC) composed of HOIP, HOIL-1L and SHARPIN is the sole E3 ubiquitin ligase that specifically generates Met1-linked ubiquitin chains. The physiological role of LUBAC-mediated Met1-Ub has been first described as activating NF-κB signaling through the Met1-Ub modification of NEMO. However, accumulating evidence shows that Met1-Ub is broadly involved in other cellular pathways including MAPK, Wnt/β-Catenin, PI3K/AKT and interferon signaling, and participates in various cellular processes including angiogenesis, protein quality control and autophagy, suggesting that Met1-Ub harbors a potent signaling capacity. Here, we review the formation and cellular functions of Met1-linked ubiquitin chains, with an emphasis on the recent advances in the cellular mechanisms by which Met1-Ub controls signaling transduction.