Corepressor MMTR/DMAP1 is an intrinsic negative regulator of CAK kinase to regulate cell cycle progression

We have previously reported that MMTR (MAT1-mediated transcriptional repressor) is a co-repressor that inhibits TFIIH-mediated transcriptional activity via interaction with MAT1 (Kang et al., 2007). Since MAT1 is a member of the CAK kinase complex that is crucial for cell cycle progression and that regulates CDK phosphorylation as well as the general transcription factor TFIIH, we investigated MMTR function in cell cycle progression. We found that MMTR over-expression delayed G1/S and G2/M transitions, whereas co-expression of MAT1 and MMTR rescued the cell growth and proliferation rate. Moreover, MMTR was required for inhibition of CAK kinase-mediated CDK1 phosphorylation. We also showed that the expression level of MMTR was modulated during cell cycle progression. Our data support the notion that MMTR is an intrinsic negative cell cycle regulator that modulates the CAK kinase activity via interaction with MAT1.

Research highlights
► Co-repressor MMTR/DMAP1 is an intrinsic negative regulator of CAK kinase.
► MMTR inhibited cell proliferation due to delays of G1/S and G2/M transitions.
► Co-expression of MAT1 and MMTR rescued both cell growth and proliferation rate.
► MMTR blocked the CAK kinase-mediated phosphorylation of CDK1.
► The expression level of MMTR was modulated during cell cycle progression.