Hexamethylene bis-acetamide-inducible protein 1 (HEXIM1)

HEXIM1 is a nuclear protein that acts primarily as an inhibitor of positive transcription elongation factor b (P-TEFb), a complex composed of CDK9 and cyclin T, and suppresses RNA polymerase II-dependent transcription elongation when bound to 7SK small nuclear RNA[1][2][3][4][5][6]. HEXIM1 contains several key regions: a proline-rich N-terminal sequence, an arginine-rich nuclear localization signal that overlaps with its main RNA-binding domain, a central region important for partner recognition, and a structured C-terminal domain that mediates dimerization. In addition to forming 7SK snRNA-dependent complexes to sequester and inhibit P-TEFb kinase activity, HEXIM1 interacts with transcription factors (e.g., the glucocorticoid receptor) via direct protein–protein contacts to modulate their activity[1]. HEXIM1 also serves as a protein hub in macromolecular complexes regulating innate immunity and has notable roles in cancer biology, where its disruption can drive increased transcription and malignant transformation and alter cellular sensitivity to inhibitors of Hsp90 or CDK9[2][3]. Its regulatory versatility extends to both transcription elongation and stimulus-dependent cellular responses.

Other names

HEXIM1CLP1EDG1HIS1MAQ1Cardiac lineage protein 1Estrogen down-regulated gene 1 proteinMenage a quatre protein 1HMBA-inducible protein 1

Suppression of P-TEFb kinase activity when bound to 7SK RNA; Indirect modulation of transcription factor activity (e.g., interference with glucocorticoid receptor signaling); Regulation of RNA polymerase II-dependent transcriptional elongation