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Figure 3. Cell-cycle regulation, CKIs studied in glioma treatment and their targets. Cell-cycle progression in cancer and the role of cyclin-dependent kinases inhibitors used in glioma studies. CDK2-cyclin E complex phosphorylates Rb leading to loss of repression of E2F factors, resulting in cell-cycle progression. Blocking the CDK2 with CKIs leads to cell-cycle arrest by preventing cell-cycle progression from G1 to S phase. Phosphorylation of carboxy-terminal domain of RNAP II by CDK9-cyclin T and CDK7-cyclin H complexes leads to transcription elongation. Blocking of CDKs 9 and 7 leads to transcription inhibition and downregulation of short-lived mRNAs, including MCL-1, c-MYC and XIAP. Single letters stand for cyclins, for instance E is cyclin E. G1: growth phase; S: DNA synthesis; G2: second growth phase; M: mitosis; G0: resting phase; CDK: cyclin-dependent kinase; MCL-1: myeloid leukaemia 1 protein; c-MYC: avian myelocytomatosis virus oncogene cellular homolog; RNAP II: RNA polymerase II; Rb: retinoblastoma protein; XIAP: X-linked inhibior of apoptosis protein; E2F: E2 transcription factor