The transcription factor USF2 is supposed to have an important role in tumor development. However, the regulatory mechanisms contributing to the function of USF2 are largely unknown. Cyclin-dependent kinase 5 (CDK5) seems to be of importance since high levels of CDK5 were found in different cancers associated with high USF2 expression. Here, we identified USF2 as a phosphorylation target of CDK5. USF2 is phosphorylated by CDK5 at two serine residues, serine 155 and serine 222. Further, phosphorylation of USF2 at these residues was shown to stabilize the protein and to regulate cellular growth and migration. Altogether, these results delineate the importance of the CDK5-USF2 interplay in cancer cells.
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http://dx.doi.org/10.3390/cancers11040523 | DOI Listing |
J Chem Phys
January 2025
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
The Effective Fragment Potential (EFP) method, a polarizable quantum mechanics-based force field for describing non-covalent interactions, is utilized to calculate protein-ligand interactions in seven inactive cyclin-dependent kinase 2-ligand complexes, employing structural data from molecular dynamics simulations to assess dynamic and solvent effects. Our results reveal high correlations between experimental binding affinities and EFP interaction energies across all the structural data considered. Using representative structures found by clustering analysis and excluding water molecules yields the highest correlation (R2 of 0.
View Article and Find Full Text PDFIUBMB Life
January 2025
Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer globally. Zinc finger protein 169 (ZNF169) holds significant importance as a transcription factor, yet its precise function in HCC remains to be elucidated. This study aims to examine the clinical importance, biological functions, and molecular pathways associated with ZNF169 in the development of HCC.
View Article and Find Full Text PDFCyclin F, a non-canonical member of the cyclin protein family, plays a critical role in regulating the precise transitions of cell-cycle events. Unlike canonical cyclins, which bind and activate cyclin-dependent kinases (CDKs), Cyclin F functions as a substrate receptor protein within the Skp1-Cullin-F box (SCF) E3 ubiquitin ligase complex, enabling the ubiquitylation of target proteins. The structural features that distinguish Cyclin F as a ligase adaptor and the mechanisms underlying its selective substrate recruitment over Cyclin A, which functions in complex with CDK2 at a similar time in the cell cycle, remain largely unexplored.
View Article and Find Full Text PDFReplication protein A (RPA) is a heterotrimeric single-strand DNA binding protein that is integral to DNA metabolism. Segregation of RPA functions in response to DNA damage is fine-tuned by hyperphosphorylation of the RPA32 subunit that is dependent on Cyclin-dependent kinase (Cdk)-mediated priming phosphorylation at the Ser-23 and Ser-29 sites. However, the mechanism of priming-driven hyperphosphorylation of RPA remains unresolved.
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January 2025
Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, China.
Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth, and neurological functions, in conjunction with mediator complex subunits 12 (MED12), MED13, and cyclin C.Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth and neurological functions,in conjunction with mediator complex subunit 12 (MED12), MED13 and cyclin C. Studying the relationship between CDK8 and cervical squamous cell carcinoma (CESC) has significant clinical implications in diagnosis, treatment, and prognosis.
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