CDK1, the Other ‘Master Regulator’ of Autophagy

Odle, Richard; Florey, Oliver; Ktistakis, Nicholas T.; Cook, Simon J.

doi:10.1016/j.tcb.2020.11.001

Cited by 42 publications

(26 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We then found that three genes, CDK1, CCNB1, and PLK1, were included in the DHA-regulated cell cycle pathway. CDK1 (also known as CDC2), the first member of cyclin-dependent kinase family, mediates multiple pathways to regulate cell division, cell autophagy, and mitochondrial respiration (41)(42)(43). It has been proven that CDK1 is connected to poor prognosis and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

Liang

Chen

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

Liang

Chen

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Even if a fraction of these sites is phosphorylated in vivo by other kinases, our data suggest that CDK1 can compensate, or complement the activity of these kinases to phosphorylate these sites in mitosis. Phosphorylation handover from mTOR kinase to CDK1 has been recently described to suppress autophagy in mitosis by targeting the same proline-directed sites in ATG13, ULK1, and ATG14 (Odle et al, 2021). Our data suggest that this handover is likely not limited to mTOR and other proline-directed kinases, and likely extends to non-proline directed kinases.…”

Section: Discussionmentioning

confidence: 99%

Cyclin A and Cks1 promote kinase consensus switching to non-proline directed CDK1 phosphorylation

al-Rawi

Korolchuk

Endicott

et al. 2022

Preprint

View full text Add to dashboard Cite

Ordered protein phosphorylation by CDKs is a key mechanism for regulating the cell cycle. How temporal order is enforced in mammalian cells remains unclear. Using a fixed cell kinase assay and phosphoproteomics, we show how CDK1 activity and non-catalytic CDK1 subunits contribute to the choice of substrate and site of phosphorylation. Increases in CDK1 activity alters substrate choice, with intermediate and low sensitivity CDK1 substrates enriched in DNA replication and mitotic functions, respectively. This activity dependence was shared between Cyclin A- and Cyclin B-CDK1. Cks1 has a proteome-wide role as an enhancer of multisite CDK1 phosphorylation. Contrary to the model of CDK1 as an exclusively proline-directed kinase, we show that Cyclin A and Cks1 promote non-proline directed phosphorylation, preferably on sites with a +3 lysine residue. Indeed, 70% of cell cycle regulated phosphorylations, where the kinase carrying out this modification has not been identified, are non-proline directed CDK1 sites.

show abstract

“…(Li et al, 2018). It is also known that CDK1 directly phosphorylates Raptor during mitosis promoting dissociation from the lysosome and subsequent inhibition of mTORC1 (Odle et al, 2021). TACC3, a kinase responsible for centrosome activity and microtubule assembly during cell division (Gergely et al, 2000;Peset and Vernos, 2008), phosphorylates Tuberin on S939 (Gómez-Baldó et al, 2010).…”

Section: Role Of Tuberin In the G2/m Transitionmentioning

confidence: 99%

Beyond Protein Synthesis; The Multifaceted Roles of Tuberin in Cell Cycle Regulation

Silva

Fong

Roye-Azar

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The ability of cells to sense diverse environmental signals, including nutrient availability and conditions of stress, is critical for both prokaryotes and eukaryotes to mount an appropriate physiological response. While there is a great deal known about the different biochemical pathways that can detect and relay information from the environment, how these signals are integrated to control progression through the cell cycle is still an expanding area of research. Over the past three decades the proteins Tuberin, Hamartin and TBC1D7 have emerged as a large protein complex called the Tuberous Sclerosis Complex. This complex can integrate a wide variety of environmental signals to control a host of cell biology events including protein synthesis, cell cycle, protein transport, cell adhesion, autophagy, and cell growth. Worldwide efforts have revealed many molecular pathways which alter Tuberin post-translationally to convey messages to these important pathways, with most of the focus being on the regulation over protein synthesis. Herein we review the literature supporting that the Tuberous Sclerosis Complex plays a critical role in integrating environmental signals with the core cell cycle machinery.

show abstract

CDK1, the Other ‘Master Regulator’ of Autophagy

Cited by 42 publications

References 82 publications

Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

Dihydroartemisinin Suppresses the Tumorigenesis and Cycle Progression of Colorectal Cancer by Targeting CDK1/CCNB1/PLK1 Signaling

Cyclin A and Cks1 promote kinase consensus switching to non-proline directed CDK1 phosphorylation

Beyond Protein Synthesis; The Multifaceted Roles of Tuberin in Cell Cycle Regulation

Contact Info

Product

Resources

About