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bioRxiv · 10.1101/2022.01.21.475743

Claspin is required for growth recovery from serum starvation through regulating the PI3K-PDK1-mTOR pathway

Yang, C.-C.·Masai, H.
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Abstract

Growth recovery from serum starvation requires the activation of PI3 kinase (PI3K)-PDK1-Akt-mTOR pathways. Claspin plays multiple important roles in regulation of DNA replication as a mediator for the cellular response to replication stress, an integral replication fork factor that facilitates replication fork progression and a factor that promotes initiation by recruiting Cdc7 kinase. Here, we report a novel role of Claspin in growth recovery from serum starvation. In the absence of Claspin, cells do not proceed into S phase and eventually die. Claspin interacts with PI3K and mTOR, and is required for activation of PI3K-PDK1-mTOR and for that of mTOR downstream factors, p70S6K and 4E-BP1, but not for p38 MAPK cascade during the recovery from serum starvation. PDK1 interacts with Claspin, notably with CKBD, in a manner dependent on phosphorylation of the latter protein, and is required for interaction of mTOR with Claspin. p53 and ROS (Reactive Oxygen Species) inhibitors increased survival of Claspin-deficient cells released from serum starvation. Thus, Claspin plays a novel role as a mediator/protein platform for nutrition-induced proliferation/survival signaling by activating the mTOR pathway.

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Yang, C.-C., Masai, H.. 2022-01-21. Claspin is required for growth recovery from serum starvation through regulating the PI3K-PDK1-mTOR pathway. https://doi.org/10.1101/2022.01.21.475743

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