From: Role of MCM2–7 protein phosphorylation in human cancer cells
Protein | Kinase | Phosphorylation site or domain | Biological and functional significance | References |
---|---|---|---|---|
MCM2 | Cdc7 | S27, S41, S139 | Suggested to be essential for initiation of DNA replication and ATPase activity of MCM complex | [16] |
Cdc7 | S5 | Promotes pre-RC assembly during cell cycle re-entry | [37] | |
Cdc7 | S40, S53, S108 | Regulates MCM2’s chromatin loading in a site-dependent manner | [19] | |
Cdc7 | S40, S108 | Unclear | [43] | |
MCM4 | Cdc7 | N-terminal | Promotes MCM4’s interaction with Cdc45 on chromatin. Suggested to be essential for initiation of DNA replication and cell growth | [17] |
MCM3 | Cdk2/CycE | T722 | Promotes MCM3’s chromatin loading. Regulates S phase checkpoint activation | [12] |
MCM4 | Cdk2 | S3, T7, S32, S54, T110 | Decreases chromatin loading of MCM complex to avoid re-replication during mitosis | [45] |
Cdk1, Cdk2 | S3, T7, T19, S32, S54, S88, T110 | Inhibits chromatin loading and helicase activity of MCM complex. Blocks DNA replication through inactivation of MCM complex | ||
MCM7 | Cdk2/CycE, Cdk1/CycB | S121 | Promotes MCM complex formation. Regulates S checkpoint activation and mitotic exit | [13] |
MCM2 | ATR | S108 | Responds to replication stress and stabilizes replication forks | [39] |
ATR | S108 | Responds to replication stress | [38] | |
MCM3 | ATM | S535 | Responds to replication stress | [38] |
ATM, ATR | S728 | Responds to replication stress | [58] | |
MCM6 | ATR | S13 | Responds to replication stress | [59] |
MCM2 | SIK1 | Unclear | Activates helicase activity of MCM complex during DNA replication | [61] |
MCM3 | DAPK | S160 | Unclear | [62] |
MCM4 | EBV-PK | T19, T110 | Blocks DNA replication through inactivation of DNA unwinding by the MCM4/6/7 complex. Leads to cell growth arrest | [26] |
MCM7 | p56Lyn | Tyr600 | Promotes MCM complex formation, chromatin loading, DNA synthesis and cancer cell proliferation. Pathologically correlates with poor survival of breast cancer patients | [23] |
Akt | Unclear | Increases MCM7’s chromatin loading and MCM complex formation. Promotes DNA replication and cancer cell proliferation | [24] | |
ILK | Unclear | Inhibits MCM7’s chromatin loading and cancer cell growth | [25] |