MNK

MAP kinase-interacting kinase MNK comprises MNK1 and MNK2, which control mRNA translation through eIF4E phosphorylation and integrate ERK1/2 or p38 MAPK signaling^[1][2]. Mechanistically, MNK binds eIF4G and phosphorylates eIF4E, linking cap-dependent translation to stress, growth-factor, cytokine, and hormone responses^[1][3]. MNK activity selectively affects translation of capped mRNAs containing a 5′-UTR hairpin, including transcripts involved in cell cycle, cancer progression, and cell survival^[3]. In cancer models, MNK1/2 support oncogenic translation, tumorigenicity, invasion, and drug resistance through eIF4E and additional substrates^[2][4]. In soft tissue sarcoma, depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity^[5]. Compared with related isoforms, MNK1a/b and MNK2a/b arise from two genes by alternative splicing and differ in C-terminal regions, MAPK-binding capacity, activity, regulation, and localization^[4]. MNK1b is constitutively active, MAPK-independent, and associated with poor prognosis in triple-negative breast cancer^[6]. For experimental applications, CGP57380, ETC-168, tomivosertib, and eFT-508 are used to block MNK-eIF4E signaling in translation, cancer, chemotherapy sensitization, and fibrosis models^[3][5][7][8].