Interferon-related developmental regulator 1 (IFRD1)

Interferon-related developmental regulator 1 (IFRD1) is a transcriptional co-activator and co-repressor expressed in multiple tissues, notably neutrophils, skeletal and cardiac muscle, brain, and pancreas[1][3][7]. It binds to and modulates key transcription factors such as MyoD, MEF2C, HDAC4, HDAC3, and the p65 subunit of NF-κB, forming complexes that affect gene transcription in processes of muscle differentiation, regeneration, and immune function[1]. IFRD1 acts as a modifier gene in cystic fibrosis, influencing the severity of lung disease through effects on neutrophil effector functions[1]. In cancer, especially hepatocellular carcinoma, IFRD1 mediates cell survival under nutrient stress by inhibiting autophagy and controlling chromatin landscape and protein synthesis; its depletion sensitizes cells to glutaminase inhibition, highlighting therapeutic potential[2]. Mutations in IFRD1 are also associated with neurodegenerative diseases such as spinocerebellar ataxia 18 and Charcot-Marie-Tooth disease type 1A[3][6][7]. Its broad range of actions reflects a central role in cellular stress responses, development, and regeneration.

Other names

TIS7PC4Nerve growth factor-inducible protein PC412-O-tetradecanoylphorbol-13-acetate-induced sequence 7Pheochromocytoma cell-4TPA-induced sequence 7

Modulation of autophagy (inhibition via ATG14/TRIM21 degradation) Regulation of chromatin accessibility through histone H1.0 turnover Enhancement or repression of key transcription factors (e.g., MyoD, MEF2C, NF-κB) Synergistic anti-tumor effect with glutaminase inhibition[2]