Last update 21 Mar 2024
CDK20
cyclin dependent kinase 20
Last update 21 Mar 2024
Basic Info
Synonyms CAK-kinase p42, CCRK, CDCH + [11] |
Introduction Required for high-level Shh responses in the developing neural tube. Together with TBC1D32, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to SHH signaling (By similarity). Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160'. |
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100 Clinical Results associated with CDK20
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100 Translational Medicine associated with CDK20
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0 Patents (Medical) associated with CDK20
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184
Literatures (Medical) associated with CDK2023 Feb 2024·Oncogene
O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation.
Article
Author: Zhongqi Feng ; Jiaxin Yin ; Zhirong Zhang ; Zhen Chen ; Luyi Huang ; Ni Tang ; Kai Wang
O-linked-β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) and ubiquitination are critical posttranslational modifications that regulate tumor development and progression. The continuous progression of the cell cycle is the fundamental cause of tumor proliferation. S-phase kinase-associated protein 2 (SKP2), an important E3 ubiquitin ligase, assumes a pivotal function in the regulation of the cell cycle. However, it is still unclear whether SKP2 is an effector of O-GlcNAcylation that affects tumor progression. In this study, we found that SKP2 interacted with O-GlcNAc transferase (OGT) and was highly O-GlcNAcylated in hepatocellular carcinoma (HCC). Mechanistically, the O-GlcNAcylation at Ser34 stabilized SKP2 by reducing its ubiquitination and degradation mediated by APC-CDH1. Moreover, the O-GlcNAcylation of SKP2 enhanced its binding ability with SKP1, thereby enhancing its ubiquitin ligase function. Consequently, SKP2 facilitated the transition from the G1-S phase of the cell cycle by promoting the ubiquitin degradation of cell cycle-dependent kinase inhibitors p27 and p21. Additionally, targeting the O-GlcNAcylation of SKP2 significantly suppressed the proliferation of HCC. Altogether, our findings reveal that O-GlcNAcylation, a novel posttranslational modification of SKP2, plays a crucial role in promoting HCC proliferation, and targeting the O-GlcNAcylation of SKP2 may become a new therapeutic strategy to impede the progression of HCC.
14 Nov 2023·medRxiv : the preprint server for health sciences
Genome-wide association study analysis of disease severity in Acne reveals novel biological insights.
Author: Zhaohui Du ; Tejaswi Iyyanki ; Samuel Lessard ; Michael Chao ; FinnGen ; Christian Asbrand ; Dany Nassar ; Katherine Klinger ; Emanuele de Rinaldis ; Shameer Khader ; Clément Chatelain
Acne vulgaris is a common skin disease that affects >85% of teenage young adults among which >8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic loci associated with increased risk of developing acne when compared to healthy individuals. However only a few studies have investigated genetic association with disease severity. GWAS of disease progression may provide a more effective approach to unveil potential disease modifying therapeutic targets. Here, we performed a multi-ethnic GWAS analysis to capture disease severity in acne patients by using individuals with normal acne as a control. Our cohort consists of a total of 2,956 participants, including 290 severe acne cases and 930 normal acne controls from FinnGen, and 522 cases and 1,214 controls from BioVU. We also performed mendelian randomization (MR), colocalization analyses and transcriptome-wide association study (TWAS) to identify putative causal genes. Lastly, we performed gene-set enrichment analysis using MAGMA to implicate biological pathways that drive disease severity in Acne. We identified two new loci associated with acne severity at the genome-wide significance level, six novel associated genes by MR, colocalization and TWAS analyses, including genes CDC7, SLC7A1, ADAM23, TTLL10, CDK20 and DNAJA4 , and 5 novel pathways by MAGMA analyses. Our study suggests that the etiologies of acne susceptibility and severity have limited overlap, with only 26% of known acne risk loci presenting nominal association with acne severity and none of the novel severity associated genes reported as associated with acne risk in previous GWAS.
19 Jul 2023·Current drug targets
The Role of CDK20 Protein in Carcinogenesis.
Review
Author: Sowmya Chivukula ; Vasavi Malkhed
Cancer is a complex disease that develops when abnormal cells divide uncontrollably as a consequence of unregulated cell cycle protein activity. Therefore, the cell cycle is crucial for maintaining homeostasis inside the cells during DNA replication and cell division. The presence of mutations within specific genes can disrupt the equilibrium within cells, ultimately leading to the growth of cancer. CDK20 (Cyclin-Dependent Kinase 20) is recently identified as a major controller of cell cycle checkpoints, which regulate cell growth and proliferation and perform a role in the development of many malignancies. CCRK (Cell-Cycle Related Kinase) has recently been renamed CDK20. Emerging studies proclaimed that the upregulation of CDK20 was identified in cancers of the ovary, brain, colon, stomach, liver, and lung. CDK20 was thought to have Cyclin-dependent activating kinase (CAK) activity for CDK2 when it is complexed with Cyclin H. Furthermore, recent studies revealed that CDK20 is involved in the Wnt, EZH2/NF-B, and KEAP1-NRF2 signaling pathways, all of which are interconnected to cancer formation and proliferation. In addition, the structure of CDK20 was predicted using ColabFold, a powerful software integrating AlphaFold's advanced AI system. The present review focuses on a systematic overview of the current knowledge on CDK20 derived from in vitro and in vivo studies and emphasizes its role in carcinogenesis. The validation comparison of the existing CDK20 AlphaFold structure with the ColabFold was found to be exceptionally fast and accurate in generating reliable models.
1
News (Medical) associated with CDK2007 Jan 2024
Alphabet's artificial intelligence (AI) start-up Isomorphic Labs has nabbed a pair of drug discovery deals with Eli Lilly and Novartis worth close to $3 billion. The announcement Sunday, coming ahead of the JP Morgan healthcare conference that kicks off January 8 in San Francisco, marks the company's first pharmaceutical partnerships.Alphabet launched Isomorphic Labs in 2021 to build on Google DeepMind's AlphaFold 2 AI technology that can be used to predict the structure of proteins in the human body, and ultimately help scientists identify new target pathways to deliver drugs for fighting disease. The latest version of AlphaFold extends its application to small molecules and nucleic acids. Researchers last year reported on the use of AlphaFold to design and create a potential CDK20 inhibitor to treat hepatocellular carcinoma.In December 2022, sources revealed that Isomorphic was holding talks with unnamed major pharmaceutical companies and expected to announce a deal in the following months, according to a report at the time.The new collaboration with Eli Lilly, which will focus on discovering small-molecule therapeutics against multiple targets, comes with a $45-million upfront payment. Isomorphic is also eligible for up to $1.7 billion in performance-based milestones, as well as royalties of up to low-double digits on net sales."We're thrilled to embark on this partnership and apply our proprietary technology platform, the next generation of AlphaFold, and access to massive computing power to Lilly's development programmes," said Isomorphic CEO Demis Hassabis.The Novartis alliance centres on uncovering small-molecule therapeutics against three undisclosed targets. The Swiss drugmaker will pay the start-up $37.5 million upfront as well as select research costs. Isomorphic could also pocket another $1.2 billion in performance-based milestone payments, plus subsequent mid-single up to low double-digit royalties on net sales.
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