Transcription factor Yin Yang 1 (YY1)

Transcription factor Yin Yang 1 (YY1) is a ubiquitously expressed zinc-finger protein of the GLI-Kruppel family that plays a fundamental role in regulating the mammalian genome. It is uniquely characterized by its dualistic capacity to act as either a transcriptional activator or a repressor, a function determined by the promoter context, its binding site, and interaction with various cofactors such as histone deacetylases (HDACs) and methyltransferases [2, 5]. YY1 is critical for essential cellular processes, including cell cycle progression, apoptosis, and chromatin remodeling, and is indispensable for normal embryonic development [3, 5]. In human disease, YY1 is frequently overexpressed in a wide range of malignancies, including breast, colon, and prostate cancers, where it acts as an oncogene by promoting cell proliferation and survival while suppressing tumor suppressors like p53 and PTEN [1, 3]. Furthermore, YY1 is a major driver of resistance to chemotherapy and immunotherapy, notably modulating the expression of CD20 to influence rituximab sensitivity in lymphoma [3, 4]. Therapeutic approaches targeting YY1 include small molecules like luteolin, nitric oxide donors that inhibit its DNA-binding activity, and strategies to downregulate its expression to sensitize tumor cells to conventional therapies [1, 4].

Other names

Yin-Yang 1Yin and Yang 1YY-1Delta transcription factorNF-E1UCRBPINO80S

Drugs targeting this molecule primarily act by inhibiting its DNA-binding activity, promoting the degradation of the YY1 protein, or downregulating its expression through the inhibition of upstream signaling pathways such as NF-kB or PI3K/AKT [1, 3, 4].