CCAAT-enhancer-binding protein homologous protein (CHOP)

CCAAT-enhancer-binding protein homologous protein (CHOP), also known as DNA damage-inducible transcript 3 (DDIT3), is a basic leucine zipper (bZIP) transcription factor that serves as a critical mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress (Uniprot P35638). Under physiological conditions, CHOP is expressed at very low levels, but it is strongly upregulated via the PERK-eIF2α-ATF4 signaling pathway when cells encounter prolonged or severe ER stress (PubMed PMID: 25447614). Once induced, CHOP functions primarily as a pro-apoptotic factor by downregulating the anti-apoptotic protein BCL-2 and promoting the expression of pro-apoptotic genes like BIM and DR5 (PubMed PMID: 18948566). Consequently, CHOP plays a pivotal role in the pathogenesis of various conditions characterized by protein misfolding, including neurodegenerative diseases, diabetes, and cardiovascular disorders (PubMed PMID: 30141331). In oncology, the DDIT3 gene is notably involved in myxoid liposarcoma, where it forms a pathognomonic fusion protein with FUS or EWSR1 (NCBI Gene ID: 1649). Therapeutic strategies targeting CHOP largely focus on small molecule inhibitors or chemical chaperones like 4-phenylbutyrate and TUDCA that mitigate ER stress to prevent pathological cell death in degenerative conditions.

Other names

DNA damage-inducible transcript 3DDIT3GADD153CHOP-10C/EBP zetaCEBPZ

Modulation of the Integrated Stress Response (ISR) to suppress CHOP-induced apoptosis or reduction of endoplasmic reticulum stress through chemical chaperoning.