Hexamethylene bisacetamide-inducible protein 1 (HEXIM1)

Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is a key transcriptional regulator that functions as a potent inhibitor of the positive transcription elongation factor b (P-TEFb). By sequestering P-TEFb (a complex of CDK9 and Cyclin T1) within the 7SK small nuclear ribonucleoprotein (snRNP) complex, HEXIM1 prevents the phosphorylation of the C-terminal domain of RNA polymerase II, thereby inhibiting transcriptional elongation. Originally identified as a protein induced by the differentiating agent hexamethylene bisacetamide (HMBA), HEXIM1 acts as a tumor suppressor in various malignancies, including breast, prostate, and melanoma, where its expression is frequently downregulated. It also functions as a co-repressor for nuclear receptors such as the estrogen receptor (ER) and androgen receptor (AR), and its presence is often required for the efficacy of anti-hormonal therapies like tamoxifen and bicalutamide. Furthermore, HEXIM1 has been identified as a robust pharmacodynamic biomarker for monitoring the target engagement of BET bromodomain inhibitors, which upregulate its expression to exert their anti-tumor effects. Beyond oncology, HEXIM1 plays roles in heart development, innate immunity via the cGAS-STING pathway, and the regulation of HIV-1 viral transcription.

Other names

CLP1EDG1HIS1MAQ1Cardiac lineage protein 1Estrogen down-regulated gene 1 proteinMenage a quatre protein 1

Sequestration of P-TEFb in the inactive 7SK snRNP complex; Co-repression of nuclear receptors (ER, AR); Induction of HEXIM1 expression by differentiating agents and epigenetic inhibitors.