One cut homeobox 3 (ONECUT3)

One cut homeobox 3 (ONECUT3) is a member of the ONECUT family of transcription factors, which are defined by their homeobox DNA-binding domain. ONECUT3 enables sequence-specific DNA binding and is predicted to regulate the transcription of target genes via interaction with RNA polymerase II[1]. It is highly expressed in certain neuronal lineages and plays a critical role in the morphological maturation, polarization, and differentiation of neurons in the vertebrate hypothalamus, especially via regulating neuron navigator-2 (NAV2) and downstream RhoA pathways[2]. ONECUT3 is also implicated in reprogramming fibroblasts to neuronal phenotypes by remodeling chromatin accessibility[1]. In disease states, high levels of ONECUT3 are associated with enhanced stemness, tumor immune evasion, and poor survival in pancreatic ductal adenocarcinoma, as well as with chromosomal instability in myelodysplastic syndromes, where it directly activates key genes such as INCENP and CDCA8 involved in mitotic progression and chromosome segregation[1][3]. At least one small molecule inhibitor, C5484617, has been identified to bind the homeobox domain of ONECUT3, inhibiting its transcriptional activity in preclinical research[3].

Other names

OC-3One cut domain family member 3OC3transcription factor ONECUT-3

Small molecule inhibition of the transcriptional activity via direct binding to the HOX/homeobox domain[3]