Cyclin-dependent kinase 5 (Cdk5) has been shown to regulate adhesion and migration of lens and corneal epithelial cells. To explore protein-protein interactions that may mediate these functions, we performed yeast two-hybrid screening on an embryonic rat lens library using Cdk5 and its regulators, p35 and p39 as baits. This screen identified an interaction between p39 and non-muscle myosin essential light chain (MLC(17)). GST pull-down experiments demonstrated that p39 binds directly to MLC(17) through a strong binding site in the N-terminal 109 amino acids of p39. Immunoprecipitation of proteins from Cos1 cells co-transfected with GFP-MLC(17) and HA-p39 confirmed that these proteins interact intracellularly. Immunofluorescence microscopy of co-transfected lens epithelial cells showed that GFP-MLC(17) and HA-p39 co-localize along cytoskeletal fibrils. Moreover, endogenous rat lens p39 co-immunoprecipitated with MLC(17) and myosin heavy chain II (MHC II), demonstrating that the interaction is physiological and serves to link p39 to the cytoskeleton.
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http://dx.doi.org/10.1016/j.bbrc.2007.01.112 | DOI Listing |
Nature
September 2024
Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p39.
View Article and Find Full Text PDFInt J Biol Macromol
March 2023
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:
Cyclin-dependent kinase 5 (CDK5) is the serine/threonine-directed kinase mainly found in the brain and plays a significant role in developing the central nervous system. Recent evidence suggests that CDK5 is activated by specific cyclins regulating its expression and activity. P35 and p39 activate CDK5, and their proteolytic degradation produces p25 and p29, which are stable products involved in the hyperphosphorylation of tau protein, a significant hallmark of various neurological diseases.
View Article and Find Full Text PDFActa Pharm Sin B
December 2022
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1) have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy. Despite the inherent advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has fallen behind that of antibody drugs. Based on docking studies between small molecule inhibitor and PD-L1 protein, changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein, which was not reported before.
View Article and Find Full Text PDFFront Mol Neurosci
November 2022
Department of Infection, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, The First Batch of Key Disciplines On Public Health in Chongqing, Chongqing, China.
Cyclin-dependent kinases 5 (Cdk5) is a special member of proline-directed serine threonine kinase family. Unlike other Cdks, Cdk5 is not directly involved in cell cycle regulation but plays important roles in nervous system functions. Under physiological conditions, the activity of Cdk5 is tightly controlled by p35 or p39, which are specific activators of Cdk5 and highly expressed in post-mitotic neurons.
View Article and Find Full Text PDFJ Biomol Struct Dyn
October 2022
College of Pharmacy, Ajman University, Abha, United Arab Emirates.
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