CDK-activating Kinase - Orthologs


CAK varies dramatically in different species. In vertebrates and Drosophilia, CAK is a trimeric protein complex consisting of Cdk7 (a Cdk-related protein kinase), cyclinH, and Mat1. The Cdk7 subunit is responsible for Cdk activation while the Mat1 subunit is responsible for transcription. The CAK trimer can be phosphorylated on the activation segment of Cdk7 subunit. However, unlike other Cdks, this phosphorylation is might not be essential for CAK activity. In the presence of Mat1, activation of CAK does not require phosphorylation of the activation segment. However in the absence of Mat1, phosphorylation of the activation segment is required for CAK activity.

In vertebrates, CAK localizes to the nucleus. This suggests that CAK is not only involved in cell-cycle regulation but is also involved in transcription. In fact, the Cdk7 subunit of vertebrate CAK phosphorylates several components of the transcriptional machinery.

In budding yeast, CAK is a monomeric protein kinase and is referred to as Cak1. Cak1 is distantly homologous to Cdks. Cak1 localizes to the cytoplasm and is responsible for Cdk activation. Budding yeast Cdk7 homolog, Kin28, does not have CAK activity.

Fission yeasts have two CAKs with both overlapping and specialized functions. The first CAK is a complex of Msc6 and Msc2. The Msc6 and Msc2 complex is related to the vertebrate Cdk7-cyclinH complex. Msc6 and Msc2 complex not only activates cell cycle Cdks but also regulates gene expression because it is part of the transcription factor TFIIH. The second fission yeast CAK, Csk1, is an ortholog of budding yeast Cak1. Csk1 can activate Cdks but is not essential for Cdk activity.

Table of Cdk-activating Kinases
Credit to: Oxford University Press "Morgan: The Cell Cycle"

Credit to: Oxford University Press "Morgan: The Cell Cycle"

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