cyclin dependent kinase 5


Summary: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.

Top Publications

  1. Slevin M, Krupinski J. Cyclin-dependent kinase-5 targeting for ischaemic stroke. Curr Opin Pharmacol. 2009;9:119-24 pubmed publisher
    ..Therefore its cell-specific pharmacological or genetic modulation using novel nanotechnology-based delivery systems could be of benefit when considering future stroke therapies. ..
  2. Freathy R, Bennett A, Ring S, Shields B, Groves C, Timpson N, et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58:1428-33 pubmed publisher
    ..Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype. ..
  3. Morel M, Authelet M, Dedecker R, Brion J. Glycogen synthase kinase-3beta and the p25 activator of cyclin dependent kinase 5 increase pausing of mitochondria in neurons. Neuroscience. 2010;167:1044-56 pubmed publisher
    ..of increased expression of glycogen synthase kinase-3beta (GSK-3beta) and of the p25 activator of cyclin dependent kinase 5 on mitochondria movements in mammalian cortical neurons and in PC12 cells...
  4. Cho D, Seo J, Park J, Jo C, Choi Y, Soh J, et al. Cyclin-dependent kinase 5 phosphorylates endothelial nitric oxide synthase at serine 116. Hypertension. 2010;55:345-52 pubmed publisher
    ..Overall, this is the first study to find that CDK5 is a physiological kinase responsible for eNOS-Ser116 phosphorylation and regulation of NO production. ..
  5. Winkler C, Illig T, Koczwara K, Bonifacio E, Ziegler A. HHEX-IDE polymorphism is associated with low birth weight in offspring with a family history of type 1 diabetes. J Clin Endocrinol Metab. 2009;94:4113-5 pubmed publisher
    ..The association of low birth weight and type 2 diabetes risk alleles of the HHEX-IDE locus is confirmed in children of mothers with type 1 diabetes. ..
  6. Kim S, Ryan T. CDK5 serves as a major control point in neurotransmitter release. Neuron. 2010;67:797-809 pubmed publisher
    ..These studies thus pinpoint CDK5 as a major control point for modulation of neurotransmitter release in mammalian neurons. ..
  7. Cardone A, Albers R, Sriram R, Pant H. Evaluation of the interaction of cyclin-dependent kinase 5 with activator p25 and with p25-derived inhibitor CIP. J Comput Biol. 2010;17:707-21 pubmed publisher
    ..Our results support the flexibility hypothesis and will be used as a basis for targeted molecular dynamics simulations. ..
  8. Lalioti V, Pulido D, Sandoval I. Cdk5, the multifunctional surveyor. Cell Cycle. 2010;9:284-311 pubmed
  9. Utreras E, Maccioni R, Gonzalez Billault C. Cyclin-dependent kinase 5 activator p35 over-expression and amyloid beta synergism increase apoptosis in cultured neuronal cells. Neuroscience. 2009;161:978-87 pubmed publisher
    ..These results represent a linkage between amyloidogenic and cdk5 pathways leading to apoptosis of neuronal cells. ..

More Information


  1. Vázquez Higuera J, Mateo I, Sanchez Juan P, Rodriguez Rodriguez E, Infante J, Berciano J, et al. No association of CDK5 genetic variants with Alzheimer's disease risk. BMC Med Genet. 2009;10:68 pubmed publisher
    ..Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between CDK5 gene and AD risk in the Dutch population exists. ..
  2. Bihaqi S, Sharma M, Singh A, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain. J Ethnopharmacol. 2009;124:409-15 pubmed publisher
    ..We investigated neuroprotective effects of aqueous extract from Convolvulus pluricaulis (CP) against aluminium chloride induced neurotoxicity in rat cerebral cortex...
  3. Mao L, Tang Q, Wang J. Regulation of extracellular signal-regulated kinase phosphorylation in cultured rat striatal neurons. Brain Res Bull. 2009;78:328-34 pubmed publisher
    ..These results indicate that the protein kinases are differentially involved in linking NMDA receptors to ERK1/2 in striatal neurons. ..
  4. Menn B, Bach S, Blevins T, Campbell M, Meijer L, Timsit S. Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models. PLoS ONE. 2010;5:e12117 pubmed publisher
    ..Our results show therefore that roscovitine protects in vivo neurons possibly through CDK5 dependent mechanisms. Altogether, our data bring new evidences for the further development of pharmacological CDK inhibitors in stroke therapy. ..
  5. Choi H, Chung S. Roscovitine increases intracellular calcium release and capacitative calcium entry in PC12 cells. Neurosci Lett. 2010;469:141-4 pubmed publisher
    ..These results suggest that Cdk5 regulates intracellular calcium homeostasis and that the dysregulation of Cdk5 may contribute to disease pathogenesis by perturbing cellular Ca(2+) signaling. ..
  6. Lopes J, Oliveira C, Agostinho P. Neurodegeneration in an Abeta-induced model of Alzheimer's disease: the role of Cdk5. Aging Cell. 2010;9:64-77 pubmed publisher
  7. Bermel C, Tönges L, Planchamp V, Gillardon F, Weishaupt J, Dietz G, et al. Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells. Mol Cell Neurosci. 2009;42:427-37 pubmed publisher
  8. Muruais G, Lalioti V, Sandoval I. The Cdk5 inhibitor roscovitine strongly inhibits glucose uptake in 3T3-L1 adipocytes without altering GLUT4 translocation from internal pools to the cell surface. J Cell Physiol. 2009;220:238-44 pubmed publisher
    ..These studies support recent evidence showing that insulin-stimulated Cdk5 is implicated in the regulation of GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. ..
  9. Choi H, Lee Y, Park K, Sung J, Lee J, Shin E, et al. Single-nucleotide polymorphisms in the promoter of the CDK5 gene and lung cancer risk in a Korean population. J Hum Genet. 2009;54:298-303 pubmed publisher
    ..59, 95% CI=1.16-2.18). These results suggest that CDK5 promoter polymorphisms contribute to the genetic susceptibility to lung cancer in the Korean population. ..
  10. Han Y, Sun A, Liu Q, Chen L, Yuan Y. [p35 and p25 expressions and Cdk5 kinase activity in primary cultured rat hippocampal neurons with X-ray exposure]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:405-7 pubmed
    ..74-/+2.27)%, P<0.01). X-ray exposure activates Cdk5 by increasing the p35 and p25 expressions in rat hippocampal neurons, and inhibition of Cdk5 activity with roscovitine can significantly protect the neurons from apoptosis. ..
  11. Kissler A, Pettersson N, Frölich A, Sigrist S, Suter B. Drosophila cdk5 is needed for locomotive behavior and NMJ elaboration, but seems dispensable for synaptic transmission. Dev Neurobiol. 2009;69:365-77 pubmed publisher
    ..futsch, the Drosophila MAP1B homolog, is also involved in NMJ morphogenesis, and analysis of the NMJ phenotype of the double mutant futsch(K68); cdk5(-) indicates that cdk5 is epistatic to futsch in this process. ..
  12. Mateo I, Vázquez Higuera J, Sanchez Juan P, Rodriguez Rodriguez E, Infante J, Garcia Gorostiaga I, et al. Epistasis between tau phosphorylation regulating genes (CDK5R1 and GSK-3beta) and Alzheimer's disease risk. Acta Neurol Scand. 2009;120:130-3 pubmed publisher
    ..08, 95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes. These data support a role for tau phosphorylation regulating genes in risk for AD. ..
  13. Tobias A, Saxena M, Lelievre V. CDK5: the "pathfinder" for new born neurons in adult hippocampus?. Cell Adh Migr. 2009;3:319-21 pubmed
  14. Jessberger S, Gage F, Eisch A, Lagace D. Making a neuron: Cdk5 in embryonic and adult neurogenesis. Trends Neurosci. 2009;32:575-82 pubmed publisher
  15. Teegarden S, Scott A, Bale T. Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling. Neuroscience. 2009;162:924-32 pubmed publisher
    ..These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world. ..
  16. Tian F, Zeng C, Ma Y, Guo T, Chen J, Chen Y, et al. Potential roles of Cdk5/p35 and tau protein in hippocampal mossy fiber sprouting in the PTZ kindling model. Clin Lab. 2010;56:127-36 pubmed
    ..Cdk5/p35 and its substrate tau protein may be involved in MFS. Understanding the molecular mechanisms underlying MFS may lead to therapeutic interventions that limit epileptogenesis. ..
  17. Long H, Zhao S, Lei T, Han J, Yuan J, Qi Y, et al. Cloning and spatio-temporal expression of porcine CDK5 and CDK5R1(p35) genes. Anim Biotechnol. 2009;20:133-43 pubmed publisher
  18. Minegishi S, Asada A, Miyauchi S, Fuchigami T, Saito T, Hisanaga S. Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39. Biochemistry. 2010;49:5482-93 pubmed publisher
    ..However, p35 and p39 show differences in degradation and cleavage rates, which may in fact underlie the distinct physiological and pathological functions of these two Cdk5 activators. ..
  19. He Y, Kastin A, Hsuchou H, Pan W. The Cdk5/p35 kinases modulate leptin-induced STAT3 signaling. J Mol Neurosci. 2009;39:49-58 pubmed publisher
    ..The results show that the activation of Cdk5 by p35 sustained leptin-induced pSTAT3 at 3-6 h. Thus, p35 is a novel modulator of leptin-induced STAT3 signaling. ..
  20. Hao Y, Pan D, Zhang M, Xu J, Li L, Wei J, et al. The neuroprotective effects of cyclin-dependent kinase-5 inhibition in mice with Niemann-Pick disease type C. J Huazhong Univ Sci Technolog Med Sci. 2009;29:324-9 pubmed publisher
    ..These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice. ..
  21. Huang E, Qu D, Zhang Y, Venderova K, Haque M, Rousseaux M, et al. The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death. Nat Cell Biol. 2010;12:563-71 pubmed publisher
  22. Zhang Z, Simpkins J. Okadaic acid induces tau phosphorylation in SH-SY5Y cells in an estrogen-preventable manner. Brain Res. 2010;1345:176-81 pubmed publisher
    ..Our results show that cdk5 is involved in OA-induced tau hyperphosphorylation, and estrogens ameliorate the tau hyperphosphorylation, which may be mediated in part by ER. ..
  23. Guan Q, Liu X, He Y, Jin L, Zhao L. Effect of cdk5 antagonist on L-dopa-induced dyskinesias in a rat model of Parkinson's disease. Int J Neurosci. 2010;120:421-7 pubmed publisher
    ..These findings suggest that up-regulated expression of Cdk5 may compensate the high levels of phosphorylation of DARPP-32 at Thr34 in LID rats. Therefore, modulation of Cdk5 for therapy of human PD should be carefully reconsidered...
  24. Mao D, Hinds P. p35 is required for CDK5 activation in cellular senescence. J Biol Chem. 2010;285:14671-80 pubmed publisher
    ..Taken together, these results suggest that p35 is at least one of the activators of CDK5 that is mobilized in the process of cellular senescence, which may provide insight into cancer cell proliferation and future cancer therapeutics. ..
  25. Fu A, Ip N. Cyclin-dependent kinase 5 links extracellular cues to actin cytoskeleton during dendritic spine development. Cell Adh Migr. 2007;1:110-2 pubmed
    ..Taken together, understanding the precise regulation of Cdk5 and its downstream targets at synapses would provide important insights into the multi-regulatory roles of Cdk5 in actin remodeling during dendritic spine development. ..
  26. Li F, Xue Y, Wang J, Fang Q, Li Y, Zhu W, et al. Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues. J Neurosci. 2010;30:10351-9 pubmed publisher
    ..Results indicate that basolateral amygdala Cdk5 activity is critical for consolidation and reconsolidation of the memories of cocaine-associated environmental cues. ..
  27. Nishimura Y, Sekine K, Chihama K, Nakajima K, Hoshino M, Nabeshima Y, et al. Dissecting the factors involved in the locomotion mode of neuronal migration in the developing cerebral cortex. J Biol Chem. 2010;285:5878-87 pubmed publisher
    ..It also uncovered roles for Fyn and PKCdelta in the early and final phases of migration, respectively. ..
  28. Zakharova E, Miller J, Unterwald E, Wade D, Izenwasser S. Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats. Neuroscience. 2009;163:890-7 pubmed publisher
  29. Zhao J, Li M, Bradfield J, Wang K, Zhang H, Sleiman P, et al. Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene. Diabetes. 2009;58:2414-8 pubmed publisher
    ..Our data show that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight. ..
  30. Sun K, Lee H, Smith M, Shah K. Direct and indirect roles of cyclin-dependent kinase 5 as an upstream regulator in the c-Jun NH2-terminal kinase cascade: relevance to neurotoxic insults in Alzheimer's disease. Mol Biol Cell. 2009;20:4611-9 pubmed publisher
    ..Finally, Cdk5 inhibition endows superior protection against neurotoxicity, suggesting that Cdk5 is a preferable therapeutic target for AD relative to JNK and c-Jun. ..
  31. Chen P, Lao C, Chen J. The D(3) dopamine receptor inhibits dopamine release in PC-12/hD3 cells by autoreceptor signaling via PP-2B, CK1, and Cdk-5. J Neurochem. 2009;110:1180-90 pubmed publisher
  32. Quaranta M, Burden A, Griffiths C, Worthington J, Barker J, Trembath R, et al. Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes. Genes Immun. 2009;10:654-8 pubmed publisher
  33. Winkler C, Bonifacio E, Grallert H, Henneberger L, Illig T, Ziegler A. BMI at age 8 years is influenced by the type 2 diabetes susceptibility genes HHEX-IDE and CDKAL1. Diabetes. 2010;59:2063-7 pubmed publisher
    ..0001) and children of nondiabetic mothers (P = 0.008). The type 2 diabetes susceptibility alleles at HHEX-IDE and CDKAL1 loci are associated with low BMI at age 8 years in children who were born large for gestational age. ..
  34. Lai K, Ip N. Recent advances in understanding the roles of Cdk5 in synaptic plasticity. Biochim Biophys Acta. 2009;1792:741-5 pubmed publisher
    ..Understanding the mechanisms by which Cdk5 regulates synaptic plasticity may therefore provide important insights in the design of novel therapeutic strategies for neurodegenerative diseases. ..
  35. White R, Ho G, Schmidt S, Scheffer I, Fischer A, Yendle S, et al. Cyclin-dependent kinase-like 5 (CDKL5) mutation screening in Rett syndrome and related disorders. Twin Res Hum Genet. 2010;13:168-78 pubmed publisher
    ..These results suggest that pathogenic CDKL5 mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions...
  36. Nakamura F, Ugajin K, Yamashita N, Okada T, Uchida Y, Taniguchi M, et al. Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice. J Comp Neurol. 2009;516:360-75 pubmed publisher
    ..Thus, Sema3A may facilitate the initial growth of CA1 apical dendrites via the activation of p35/Cdk5, which may in turn signal hippocampal development. ..
  37. Beauchard A, Laborie H, Rouillard H, Lozach O, Ferandin Y, Le Guevel R, et al. Synthesis and kinase inhibitory activity of novel substituted indigoids. Bioorg Med Chem. 2009;17:6257-63 pubmed publisher
    ..18 and 0.1 microM, respectively), CK1 (0.6 microM and 0.13 microM) and GSK3 (0.04 microM and 0.36 microM). ..
  38. Wen J, Rönn T, Olsson A, Yang Z, Lu B, Du Y, et al. Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS ONE. 2010;5:e9153 pubmed publisher
  39. Soutar M, Thornhill P, Cole A, Sutherland C. Increased CRMP2 phosphorylation is observed in Alzheimer's disease; does this tell us anything about disease development?. Curr Alzheimer Res. 2009;6:269-78 pubmed
  40. Imahori K. The biochemical study on the etiology of Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86:54-61 pubmed
    ..Finally we have identified oligomeric aggregation of Abeta protein named Amylospheroid is highly potent to degenerate neuronal cells both in vitro and in vivo systems. ..
  41. Xie W, He Y, Yang Y, Li Y, Kang K, Xing B, et al. Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the delta-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci. 2009;29:3551-64 pubmed publisher
  42. Kuo H, Hsu F, Chiang M, You S, Chen M, Lo M, et al. The role of Cdk5 in retinoic acid-induced apoptosis of cervical cancer cell line. Chin J Physiol. 2009;52:23-30 pubmed
    ..In conclusion, we provide evidence to suggest that Cdk5 and p35 might play important roles in RA-induced HeLa apoptosis. ..
  43. Lalioti V, Muruais G, Dinarina A, van Damme J, Vandekerckhove J, Sandoval I. The atypical kinase Cdk5 is activated by insulin, regulates the association between GLUT4 and E-Syt1, and modulates glucose transport in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 2009;106:4249-53 pubmed publisher
    ..These studies elucidate a previously unknown activity of Cdk5 and demonstrate the involvement of this kinase in the regulation of insulin-dependent glucose uptake in adipocytes. ..
  44. Takahashi S, Ohshima T, Hirasawa M, Pareek T, Bugge T, Morozov A, et al. Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration. Am J Pathol. 2010;176:320-9 pubmed publisher
  45. Hu C, Zhang R, Wang C, Wang J, Ma X, Lu J, et al. PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population. PLoS ONE. 2009;4:e7643 pubmed publisher
    ..0006). The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively. ..
  46. Sanchez A, Flamini M, Fu X, Mannella P, Giretti M, Goglia L, et al. Rapid signaling of estrogen to WAVE1 and moesin controls neuronal spine formation via the actin cytoskeleton. Mol Endocrinol. 2009;23:1193-202 pubmed publisher
  47. Zheng Y, Amin N, Hu Y, Rudrabhatla P, Shukla V, Kanungo J, et al. A 24-residue peptide (p5), derived from p35, the Cdk5 neuronal activator, specifically inhibits Cdk5-p25 hyperactivity and tau hyperphosphorylation. J Biol Chem. 2010;285:34202-12 pubmed publisher
    ..These results suggest that p5 peptide may be a unique and useful candidate for therapeutic studies of certain neurodegenerative diseases. ..
  48. Dong H, Lin W, Wu J, Chen T. Flavonoids activate pregnane x receptor-mediated CYP3A4 gene expression by inhibiting cyclin-dependent kinases in HepG2 liver carcinoma cells. BMC Biochem. 2010;11:23 pubmed publisher
    ..These results may have important implications on the pharmacokinetics of drugs co-administered with herbal remedy and herbal-drug interactions. ..
  49. Virtudazo E, Kawamoto S, Ohkusu M, Aoki S, Sipiczki M, Takeo K. The single Cdk1-G1 cyclin of Cryptococcus neoformans is not essential for cell cycle progression, but plays important roles in the proper commitment to DNA synthesis and bud emergence in this yeast. FEMS Yeast Res. 2010;10:605-18 pubmed publisher
    ..Also, that C. neoformans had only a single Cdk1-G1 cyclin highlighted the importance of keeping in order the commitment to the initiation of DNA synthesis first and then that of budding, as discussed. ..
  50. Hawasli A, Koovakkattu D, Hayashi K, Anderson A, Powell C, Sinton C, et al. Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. PLoS ONE. 2009;4:e5808 pubmed publisher
    ..These findings indicate that Cdk5 regulates synaptic plasticity, controls neuronal and behavioral stimulus-induced excitability and may be a novel pharmacological target for cognitive and anticonvulsant therapies. ..
  51. Brinkkoetter P, Wu J, Ohse T, Krofft R, Schermer B, Benzing T, et al. p35, the non-cyclin activator of Cdk5, protects podocytes against apoptosis in vitro and in vivo. Kidney Int. 2010;77:690-9 pubmed publisher
    ..Our study shows that p35 does not affect glomerulogenesis but controls podocyte survival following injury, in part, by regulating Bcl-2 expression. ..
  52. Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, Ohnaka K, et al. Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes. 2009;58:1690-9 pubmed publisher
    ..The strength of association was more prominent in the Japanese population than in Europeans for more than half of the confirmed type 2 diabetes loci. ..
  53. Lozano J, Schatt P, Verge V, Gobinet J, Villey V, Peaucellier G. CDK5 is present in sea urchin and starfish eggs and embryos and can interact with p35, cyclin E and cyclin B3. Mol Reprod Dev. 2010;77:449-61 pubmed publisher
    ..However, p35 mRNA expression was found to begin only at the end of the blastula stage, and the protein was undetectable at any embryonic stage, suggesting a neuronal role beginning in late larval stages. ..