The eIF5-mimic protein 5MP1: a regulator of translation stringency and a multifaceted oncogene

Accurate initiation of eukaryotic translation is essential for proteome integrity, yet the process is intrinsically challenged by the potential use of non-AUG start codons. The eIF5-mimic protein 5MP1 (also known as BZW2) has emerged as a pivotal regulator that enhances stringency in start codon selection by competing with eIF5 and eIF2B for binding to eIF2 and eIF3. This competition suppresses non-AUG and repeat-associated non-AUG (RAN) translation and remodels the dynamics of the scanning preinitiation complex. Beyond its biochemical role, accumulating evidence since the first report of BZW1/5MP2 as an oncogene in 2009 indicates that 5MP1/2 proteins promote proliferation, metastasis, and poor prognosis across diverse cancer types. However, the downstream effectors and mechanistic pathways linking translation control to tumorigenesis remain incompletely defined. This review summarizes current biochemical understanding of 5MP1 in translation initiation and synthesizes evidence supporting its tumor-promoting activities, outlining key questions and future directions.