CDK7
Cyclin-dependent kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (39 kDa protein kinase) (p39 Mo15) (CDK-activating kinase 1) (Cell division protein kinase 7) (Serine/threonine-protein kinase 1) (TFIIH basal transcription factor complex kinase subunit) [CAK] [CAK1] [CDKN7] [MO15] [STK1]
Publications[править]
Despite their supposedly terminally-differentiated quiescent status, many neurons in Alzheimer disease display an ectopic re-expression of cell-cycle related proteins. In the highly regulated process of cell cycle, cyclin-dependent kinase 7 (Cdk7) plays a crucial role as a Cdk-activating kinase and activates all of the major Cdk-cyclin substrates. In this study, we demonstrate that Cdk7 immunoreactivity is significantly elevated in susceptible hippocampal neurons of Alzheimer disease patients in comparison with age-matched controls. Notably, the expression of Cdk7 is age-dependent, with decreased levels between the ages of 54 and 65 years and after the age of 78. While the Cdk7 levels in Alzheimer disease patients are higher than controls within each age group, the difference is greatest between ages 54-65 where disease susceptibility and/or progression is likely more related to genetic factors.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Cell Cycle
- Child
- Cyclin-Dependent Kinases
- Cytoplasm
- Hippocampus
- Humans
- Middle Aged
- Neurons
- Protein-Serine-Threonine Kinases
- Reference Values
During early postnatal development, cardiomyocytes, which comprise about 80% of ventricular mass and volume, become phenotypically developed to facilitate their contractile functions and terminally differentiated to grow only in size but not in cell number. These changes are due to the expression of contractile proteins as well as the regulation of intracellular signal transduction proteins. In this study, the expression patterns of several protein kinases involved in various cardiac functions and cell-cycle control were analyzed by Western blotting of ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats. The expression level of cAMP-dependent protein kinase was slightly decreased (20%) over the first year, whereas no change was detected in cGMP-dependent protein kinase I. Calmodulin-dependent protein kinase II, which is involved in Ca2 uptake into the sarcoplasmic reticulum, was increased as much as ten-fold. To the contrary, the expressions of protein kinase C-alpha and iota declined 77% with age. Cyclin-dependent protein kinases (CDKs) such as CDK1, CDK2, CDK4, and CDK5, which are required for cell-cycle progression, abruptly declined to almost undetectable levels after 10-20 days of age. In contrast, other CDK-related kinases, such as CDK8 or Kkialre, did not change significantly or increased up to 50% with age, respectively. Protein kinases implicated in CDK regulation such as CDK7 and Wee1 were either slightly increased in expression or did not change significantly. All of the proteins that were detected in ventricular extracts were also identified in isolated cardiac myocytes in equivalent amounts and analyzed for their relative expression in ten other adult rat tissues.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Blotting, Western
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Calcium-Calmodulin-Dependent Protein Kinases
- Cell Cycle Proteins
- Cell Extracts
- Cyclic Nucleotide-Regulated Protein Kinases
- Cyclin-Dependent Kinases
- Heart Ventricles
- Male
- Molecular Sequence Data
- Myocardium
- Nuclear Proteins
- Organ Specificity
- Protein Kinase C
- Protein-Tyrosine Kinases
- Rats
- Rats, Sprague-Dawley
- Second Messenger Systems