Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene. [5] [6]
The protein encoded by this gene (p35) is a neuron-specific activator of cyclin-dependent kinase 5 (CDK5); the activation of CDK5 is required for proper development of the central nervous system. The p35 form of this protein is proteolytically cleaved by calpain, generating a p25 form. The cleavage of p35 into p25 results in relocalization of the protein from the cell periphery to nuclear and perinuclear regions. P25 deregulates CDK5 activity by prolonging its activation and changing its cellular location. The p25 form accumulates in the brain neurons of patients with Alzheimer's disease. This accumulation correlates with an increase in CDK5 kinase activity, and may lead to aberrantly phosphorylated forms of the microtubule-associated protein tau, which contributes to Alzheimer's disease. [6]
In melanocytic cells CDK5R1 gene expression may be regulated by MITF. [7]
CDK5R1 has been shown to interact with:
Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzymes play a crucial role in the regulation of eukaryotic cell cycle and transcription, as well as DNA repair, metabolism, and epigenetic regulation, in response to several extracellular and intracellular signals. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. The catalytic activities of CDKs are regulated by interactions with CDK inhibitors (CKIs) and regulatory subunits known as cyclins. Cyclins have no enzymatic activity themselves, but they become active once they bind to CDKs. Without cyclin, CDK is less active than in the cyclin-CDK heterodimer complex. CDKs phosphorylate proteins on serine (S) or threonine (T) residues. The specificity of CDKs for their substrates is defined by the S/T-P-X-K/R sequence, where S/T is the phosphorylation site, P is proline, X is any amino acid, and the sequence ends with lysine (K) or arginine (R). This motif ensures CDKs accurately target and modify proteins, crucial for regulating cell cycle and other functions. Deregulation of the CDK activity is linked to various pathologies, including cancer, neurodegenerative diseases, and stroke.
Cortactin is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton, especially the actin cortex around the cellular periphery. It is present in all cell types. When activated, it will recruit Arp2/3 complex proteins to existing actin microfilaments, facilitating and stabilizing nucleation sites for actin branching. Cortactin is important in promoting lamellipodia formation, invadopodia formation, cell migration, and endocytosis.
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.
CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.
Megakaryocyte-associated tyrosine-protein kinase is an enzyme that in humans is encoded by the MATK gene.
PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDK11B gene.
Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene.
Serine/threonine-protein kinase PCTAIRE-1 is an enzyme that in humans is encoded by the CDK16 gene.
Mitogen-activated protein kinase 12 is an enzyme that in humans is encoded by the MAP3K12 gene.
Cell division protein kinase 3 is an enzyme that in humans is encoded by the CDK3 gene.
CDK5 regulatory subunit-associated protein 3 is a protein that in humans is encoded by the CDK5RAP3 gene.
Vinexin is a protein that in humans is encoded by the SORBS3 gene.
CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.
Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene.
Cyclin-dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. It was discovered 15 years ago, and it is saliently expressed in post-mitotic central nervous system neurons (CNS).
Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 (LMTK2) is an enzyme that in humans is encoded by the LMTK2 gene.
Gentry Namón Patrick is an American biologist and Professor of Neurobiology at the University of California, San Diego. His research investigates the mechanisms that underpin synaptic activity in the central nervous system. He is interested in learning, the formation of memories and the processes that cause Alzheimer's disease and Parkinson's disease.