Biology:CDK5R1
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Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.[1][2]
Function
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.[2]
In melanocytic cells CDK5R1 gene expression may be regulated by MITF.[3]
Interactions
CDK5R1 has been shown to interact with:
- Actinin, alpha 1[4]
- Amphiphysin,[5]
- Beta-catenin,[6]
- CAMK2A,[7]
- CDK5RAP2,[8]
- Cyclin-dependent kinase 5,[9][10]
- Protein SET,[11]
See also
- CDK5RAP1
- CDK5RAP2
- CDK5RAP3
References
- ↑ "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature 371 (6496): 419–23. October 1994. doi:10.1038/371419a0. PMID 8090221. Bibcode: 1994Natur.371..419T.
- ↑ 2.0 2.1 "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8851.
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ "Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35". J. Biol. Chem. 277 (35): 31988–93. August 2002. doi:10.1074/jbc.M201161200. PMID 12084709.
- ↑ "Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2". J. Biol. Chem. 276 (11): 8104–10. March 2001. doi:10.1074/jbc.M008932200. PMID 11113134.
- ↑ "p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction". Eur. J. Neurosci. 13 (2): 241–7. January 2001. doi:10.1046/j.1460-9568.2001.01376.x. PMID 11168528.
- ↑ "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner". J. Neurosci. 22 (18): 7879–91. September 2002. doi:10.1523/JNEUROSCI.22-18-07879.2002. PMID 12223541.
- ↑ "Identification of a common protein association region in the neuronal Cdk5 activator". J. Biol. Chem. 275 (41): 31763–9. October 2000. doi:10.1074/jbc.M004358200. PMID 10915792.
- ↑ "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood 97 (12): 3763–7. June 2001. doi:10.1182/blood.V97.12.3763. PMID 11389014.
- ↑ "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell 8 (3): 657–69. September 2001. doi:10.1016/S1097-2765(01)00343-4. PMID 11583627.
- ↑ "The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity". J. Biol. Chem. 277 (9): 7324–32. March 2002. doi:10.1074/jbc.M107270200. PMID 11741927.
Further reading
- "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2): 91–6. 2003. doi:10.1080/13550280290167885. PMID 12491158.
- "The neuronal cyclin-dependent kinase 5 activator p35Nck5a and Cdk5 activity in monocytic cells". Leuk. Lymphoma 44 (2): 235–40. 2003. doi:10.1080/1042819021000030009. PMID 12688339.
- "A novel tau-tubulin kinase from bovine brain". FEBS Lett. 372 (1): 59–64. 1995. doi:10.1016/0014-5793(95)00955-9. PMID 7556643.
- "An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator". J. Biol. Chem. 270 (45): 26897–903. 1995. doi:10.1074/jbc.270.45.26897. PMID 7592934.
- "Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality". Neuron 18 (1): 29–42. 1997. doi:10.1016/S0896-6273(01)80044-1. PMID 9010203.
- "Identification of functional domains in the neuronal Cdk5 activator protein". J. Biol. Chem. 272 (9): 5703–8. 1997. doi:10.1074/jbc.272.9.5703. PMID 9038181.
- "Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". J. Biol. Chem. 274 (7): 4027–35. 1999. doi:10.1074/jbc.274.7.4027. PMID 9933594.
- "Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration". Nature 402 (6762): 615–22. 2000. doi:10.1038/45159. PMID 10604467.
- "Cloning of three novel neuronal Cdk5 activator binding proteins". Gene 242 (1–2): 285–94. 2000. doi:10.1016/S0378-1119(99)00499-0. PMID 10721722.
- "Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase". Curr. Biol. 10 (7): 363–72. 2000. doi:10.1016/S0960-9822(00)00411-5. PMID 10753743.
- "Neurotoxicity induces cleavage of p35 to p25 by calpain". Nature 405 (6784): 360–4. 2000. doi:10.1038/35012636. PMID 10830966. Bibcode: 2000Natur.405..360L.
- "Identification of a common protein association region in the neuronal Cdk5 activator". J. Biol. Chem. 275 (41): 31763–9. 2000. doi:10.1074/jbc.M004358200. PMID 10915792.
- "Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2". J. Biol. Chem. 276 (11): 8104–10. 2001. doi:10.1074/jbc.M008932200. PMID 11113134.
- "p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction". Eur. J. Neurosci. 13 (2): 241–7. 2001. doi:10.1046/j.1460-9568.2001.01376.x. PMID 11168528.
- "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood 97 (12): 3763–7. 2001. doi:10.1182/blood.V97.12.3763. PMID 11389014.
- "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell 8 (3): 657–69. 2001. doi:10.1016/S1097-2765(01)00343-4. PMID 11583627.
- "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. 276 (52): 49043–52. 2002. doi:10.1074/jbc.M105599200. PMID 11604394.
- "The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity". J. Biol. Chem. 277 (9): 7324–32. 2002. doi:10.1074/jbc.M107270200. PMID 11741927.
- "Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29". J. Biol. Chem. 277 (10): 8054–60. 2002. doi:10.1074/jbc.M109645200. PMID 11784720.
External links
- Human CDK5R1 genome location and CDK5R1 gene details page in the UCSC Genome Browser.
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