Homeobox protein Meis2 (MEIS2)

Homeobox protein Meis2 is a highly conserved TALE-class transcription factor essential for regulation of developmental programs across multiple organ systems, including the brain, heart, craniofacial structures, and hematopoietic tissues. In adults, MEIS2 continues to regulate differentiation and cell cycle genes, with dysregulation playing key roles in cancer, where it can function both oncogenically (promoting cell proliferation and survival) and as a tumor suppressor depending on cellular context. MEIS2 exerts its functions by partnering with other homeodomain proteins (notably HOX and PBX proteins) to orchestrate context-specific gene expression. In cancer, MEIS2 affects tumor cell proliferation, apoptosis, metastasis, and drug response, and is itself regulated by diverse mechanisms including microRNAs and alternative splicing. Pathogenic variants or deletions in MEIS2 are implicated in congenital syndromes involving cleft palate, cardiac anomalies, and neurodevelopmental disorders. Therapeutic modulation of MEIS2, especially in oncology, is under investigation through direct and indirect targeting strategies that leverage its interaction with ubiquitin ligase complexes and transcriptional networks.

Other names

Meis homeobox 2MEIS2MRG1HsT18361Meis1-related protein 1CPCMRMeis1-related gene 1TALE homeobox protein Meis2meis1 homolog 2

Drugs like lenalidomide compete with MEIS2 for binding to cereblon (CRBN), altering CRBN's E3 ubiquitin ligase substrate specificity, preventing MEIS2 degradation and promoting degradation of other targets; BET inhibitors downregulate MEIS2 expression; CDK inhibitors (such as Seliciclib) induce apoptosis, with MEIS2 knockdown increasing drug efficacy.