Hes family bHLH transcription factor 3 (HES3)

Hes family bHLH transcription factor 3 (HES3) is a member of the Hes gene family encoding a nuclear protein characterized by a basic helix-loop-helix (bHLH) DNA-binding domain and involved predominantly in transcriptional repression[2][3][5]. HES3 binds to N-box DNA motifs and represses gene expression by direct DNA binding or via interactions with co-repressors. It plays critical roles in regulating neurogenesis, neural cell differentiation, and self-renewal of neural stem cells, and is regulated in part by non-canonical Notch signaling via STAT3 phosphorylation[2]. Mutations or loss of HES3 in animal models lead to abnormal brain development. In cancer, HES3 is overexpressed in non-small cell lung cancer (NSCLC) and correlates with advanced disease, increased proliferation, invasion, metastasis, and shorter survival, potentially via regulation of Cyclin D1, Cyclin D3, and MMP7[2]. While it is a marker of both neural progenitor cells and aggressive lung carcinoma, there are currently no therapeutic agents directly targeting HES3 in clinical use.

Other names

Transcription factor HES-3BHLHB43bHLHb43Class B basic helix-loop-helix protein 43Hairy and enhancer of split 3