CDK-activating kinase assembly factor MAT1 (MAT1)

CDK-activating kinase assembly factor MAT1 (also known as MNAT1) is an essential protein component of the CDK-activating kinase (CAK) complex, which also includes cyclin H and CDK7[1][2][3]. MAT1 stabilizes the interaction between CDK7 and cyclin H, forming a heterotrimeric complex fundamental for both cell cycle progression and transcription initiation by RNA polymerase II[2][3]. Within the CAK complex, MAT1 enhances the kinase’s ability to phosphorylate CDKs and the C-terminal domain (CTD) of RNA polymerase II, thereby regulating entry into cell cycle and transcriptional activity[1][2][3]. CAK, and specifically the MAT1 subunit, has gained therapeutic interest, particularly for targeting cancers highly dependent on transcriptional regulation; small molecule inhibitors such as THZ1 covalently inhibit CDK7 activity within CAK[2][3]. Defects or dysregulation in MAT1-containing complexes are linked to diseases including cancer and Cockayne syndrome[1].

Other names

MNAT1CAP35RNF66p35p36TFB3Menage a trois 1 (CAK assembly factor)RING finger protein MAT1Cyclin-G1-interacting proteinCyclin H assembly factorCDK-activating kinase assembly factorCyclin G1 interacting proteinMenage a trois-like protein 1

Irreversible inhibition of kinase activity (by targeting CDK7 active site, e.g., THZ1) Disruption of cell cycle progression and transcription by RNA polymerase II