Biomaterial Database

Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). 1999

K Hiromura, and J W Pippin, and M L Fero, and J M Roberts, and S J Shankland

Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, Washington 98195-6521, USA.

Proliferation and apoptosis are increased in many types of inflammatory diseases. A role for the cyclin kinase inhibitor p27(Kip1) (p27) in limiting proliferation has been shown. In this study, we show that p27(-/-) mesangial cells and fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when deprived of growth factors. Apoptosis was rescued by restoration of p27 expression. Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E-CDK2 activity, was increased in serum-starved p27(-/-) cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant-negative mutant, inhibited apoptosis. Our results show that a new biological function for the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2 activity. These results suggest that CDK inhibitors are necessary for coordinating the cell cycle and cell-death programs so that cell viability is maintained during exit from the cell cycle.

UI	MeSH Term	Description	Entries
D008869	Microtubule-Associated Proteins	High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.	Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D005920	Glomerular Mesangium	The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.	Mesangium, Glomerular,Mesangial Extracellular Matrix,Extracellular Matrices, Mesangial,Extracellular Matrix, Mesangial,Glomerular Mesangiums,Matrices, Mesangial Extracellular,Matrix, Mesangial Extracellular,Mesangial Extracellular Matrices,Mesangiums, Glomerular
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D016147	Genes, Tumor Suppressor	Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.	Antioncogenes,Cancer Suppressor Genes,Emerogenes,Genes, Cancer Suppressor,Genes, Growth Suppressor,Genes, Metastasis Suppressor,Growth Suppressor Genes,Metastasis Suppressor Genes,Tumor Suppressor Genes,Anti-Oncogenes,Genes, Onco-Suppressor,Oncogenes, Recessive,Tumor Suppressing Genes,Anti Oncogenes,Anti-Oncogene,Antioncogene,Cancer Suppressor Gene,Emerogene,Gene, Cancer Suppressor,Gene, Growth Suppressor,Gene, Metastasis Suppressor,Gene, Onco-Suppressor,Gene, Tumor Suppressing,Gene, Tumor Suppressor,Genes, Onco Suppressor,Genes, Tumor Suppressing,Growth Suppressor Gene,Metastasis Suppressor Gene,Onco-Suppressor Gene,Onco-Suppressor Genes,Oncogene, Recessive,Recessive Oncogene,Recessive Oncogenes,Suppressor Gene, Cancer,Suppressor Gene, Growth,Suppressor Gene, Metastasis,Suppressor Genes, Cancer,Suppressor Genes, Growth,Suppressor Genes, Metastasis,Tumor Suppressing Gene,Tumor Suppressor Gene
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017209	Apoptosis	A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.	Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017346	Protein Serine-Threonine Kinases	A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.	Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D042846	CDC2-CDC28 Kinases	A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE, S CEREVISIAE and the CDC2 PROTEIN KINASE found in mammalian species.	CDC2-Related Kinases,CDC2+-CDC28-related Protein Kinase,CDC2-Related Kinase,CDC28-Related Kinases,CDC2 CDC28 Kinases,CDC2 Related Kinase,CDC2 Related Kinases,CDC2+ CDC28 related Protein Kinase,CDC28 Related Kinases
D050760	Cyclin-Dependent Kinase Inhibitor p27	A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.	CDK Inhibitor p27,CDKN1B Protein,CDKN4 Protein,Cyclin-Dependent Kinase Inhibitor 1B,p27 CDK Inhibitor,p27 Kip1 Protein,p27Kip1 Protein,CDK Inhibitor, p27,Cyclin Dependent Kinase Inhibitor 1B,Cyclin Dependent Kinase Inhibitor p27,Kip1 Protein, p27,p27, CDK Inhibitor