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Gene Review

Cdk5r1  -  cyclin-dependent kinase 5, regulatory...

Rattus norvegicus

Synonyms: CDK5 activator 1, Cdk5r, Cyclin-dependent kinase 5 activator 1, Cyclin-dependent kinase 5 regulatory subunit 1, TPKII regulatory subunit, ...
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Disease relevance of Cdk5r1

  • These results, therefore, provide a strategy to address, and possibly ameliorate, the pathology of neurodegenerative diseases that may be a consequence of aberrant p25 activation of Cdk5, without affecting 'normal' Cdk5 activity [1].
  • In rats without IT, the p35 levels slightly decreased after ischemia or reperfusion, whereas the levels of p25 (the truncated form of p35) were much higher than those in sham control rats after ischemia and remained elevated during reperfusion [2].
  • Here, the levels of two calpain-specific substrates, p35 protein and eukaryotic initiation factor 4G (eIF4G), as well as its physiological regulator calpastatin, were investigated in a rat model of transient global cerebral ischemia with or without ischemic tolerance (IT) [2].
  • In conclusion, pre-treatment with ASA induces tolerance against hypoxia/reoxygenation damage in spinal cord cultures by restoring Cdk5 and p35 protein expression [3].
  • Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases beta-amyloid toxicity in cortical neurons [4].

Psychiatry related information on Cdk5r1


High impact information on Cdk5r1

  • These results suggest that Cdk5/p35 may be a drug target for the regulation of glucose-stimulated insulin secretion [6].
  • Immunohistochemistry was used to localize p35 to a raphe of primitive glial ependymal cells in the median one-third of the floor plate in the central nervous system (CNS) of rat embryos [7].
  • We show that neuronal infections with Cdk5 inhibitory peptide (CIP) selectively inhibit p25/Cdk5 activity and suppress the aberrant tau phosphorylation in cortical neurons [1].
  • Activated tyrosine kinases therefore regulate the association of Shc proteins with p23 and may thereby control the stimulation of an Shc-mediated signal transduction pathway [8].
  • A dominant-negative mutant of cdk5 blocked both p35- and p39-induced neurite extension as well as basic fibroblast growth factor (bFGF)-induced neuronal differentiation [9].

Chemical compound and disease context of Cdk5r1

  • Our results showed that broad-spectrum inhibitors of the caspases, namely the baculovirus p35 gene and the peptide benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, effectively inhibit the death of both naive and neuronal PC12 cells [10].

Biological context of Cdk5r1


Anatomical context of Cdk5r1


Associations of Cdk5r1 with chemical compounds

  • Different factors, such as maturation state of neurons or desensitization properties of non-NMDA receptors, may determine which receptor predominantly mediates the effect of glutamate on p35 cleavage [19].
  • The data suggest that both NMDA and non-NMDA receptors are able to induce p35 cleavage [19].
  • Treatment of brain homogenate with okadaic acid in the presence of ATP led to accumulation of p35 phosphorylated also by a kinase that was not inhibited by roscovitine [11].
  • The phosphatase inhibitor okadaic acid induced p35 degradation in neuronal cultures which was sensitive to the proteasome inhibitor lactacystin [11].
  • Cyclothiazide (CTZ), an inhibitor of AMPA receptor desensitization, enhanced glutamate-induced p35 cleavage [19].

Physical interactions of Cdk5r1

  • Activity and regulation of p35/Cdk5 kinase complex [20].

Enzymatic interactions of Cdk5r1


Regulatory relationships of Cdk5r1


Other interactions of Cdk5r1


Analytical, diagnostic and therapeutic context of Cdk5r1

  • Although IT did not promote significant changes in p35 and p25 levels, it induced a slight increase in calpastatin and eIF4G levels in the hippocampal subregions after 4 h of reperfusion [2].
  • The p35 recovered in the pellet after centrifugation could then be cleaved to p25 by purified calpain [22].
  • To determine whether the two activators are expressed in different cells throughout the nervous system and during development, we compared the tissue distributions of cdk5, p35, and p39 mRNAs in the rat using in situ hybridization [23].
  • In addition to the induction of mRNA expression, the total Cdk5 and p35-associated kinase activity in muscle increased prominently after nerve denervation [24].
  • Prolongation of rat intestinal allograft survival by administration of donor interleukin-12 p35-silenced bone marrow-derived dendritic cells [21].


  1. A Cdk5 inhibitory peptide reduces tau hyperphosphorylation and apoptosis in neurons. Zheng, Y.L., Kesavapany, S., Gravell, M., Hamilton, R.S., Schubert, M., Amin, N., Albers, W., Grant, P., Pant, H.C. EMBO J. (2005) [Pubmed]
  2. Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model. Garc??a-Bonilla, L., Burda, J., Pi??eiro, D., Ayuso, I., G??mez-Calcerrada, M., Salinas, M. Neurochem. Res. (2006) [Pubmed]
  3. Aspirin provides cyclin-dependent kinase 5-dependent protection against subsequent hypoxia/reoxygenation damage in culture. Vartiainen, N., Keksa-Goldsteine, V., Goldsteins, G., Koistinaho, J. J. Neurochem. (2002) [Pubmed]
  4. Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases beta-amyloid toxicity in cortical neurons. Li, G., Faibushevich, A., Turunen, B.J., Yoon, S.O., Georg, G., Michaelis, M.L., Dobrowsky, R.T. J. Neurochem. (2003) [Pubmed]
  5. Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells. Nath, R., Davis, M., Probert, A.W., Kupina, N.C., Ren, X., Schielke, G.P., Wang, K.K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  6. Cdk5-dependent regulation of glucose-stimulated insulin secretion. Wei, F.Y., Nagashima, K., Ohshima, T., Saheki, Y., Lu, Y.F., Matsushita, M., Yamada, Y., Mikoshiba, K., Seino, Y., Matsui, H., Tomizawa, K. Nat. Med. (2005) [Pubmed]
  7. The EGF receptor kinase substrate p35 in the floor plate of the embryonic rat CNS. McKanna, J.A., Cohen, S. Science (1989) [Pubmed]
  8. Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases. McGlade, J., Cheng, A., Pelicci, G., Pelicci, P.G., Pawson, T. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. Role of cyclins in neuronal differentiation of immortalized hippocampal cells. Xiong, W., Pestell, R., Rosner, M.R. Mol. Cell. Biol. (1997) [Pubmed]
  10. Need for caspases in apoptosis of trophic factor-deprived PC12 cells. Haviv, R., Lindenboim, L., Li, H., Yuan, J., Stein, R. J. Neurosci. Res. (1997) [Pubmed]
  11. Influence of phosphorylation of p35, an activator of cyclin-dependent kinase 5 (cdk5), on the proteolysis of p35. Kerokoski, P., Suuronen, T., Salminen, A., Soininen, H., Pirttilä, T. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  12. Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18. Fletcher, A.I., Shuang, R., Giovannucci, D.R., Zhang, L., Bittner, M.A., Stuenkel, E.L. J. Biol. Chem. (1999) [Pubmed]
  13. Developmental regulation of the proteolysis of the p35 cyclin-dependent kinase 5 activator by phosphorylation. Saito, T., Onuki, R., Fujita, Y., Kusakawa, G., Ishiguro, K., Bibb, J.A., Kishimoto, T., Hisanaga, S. J. Neurosci. (2003) [Pubmed]
  14. Expression of cyclin-dependent kinase 5 and its activator p35 in models of induced apoptotic death in neurons of the substantia nigra in vivo. Neystat, M., Rzhetskaya, M., Oo, T.F., Kholodilov, N., Yarygina, O., Wilson, A., El-Khodor, B.F., Burke, R.E. J. Neurochem. (2001) [Pubmed]
  15. Implication of cyclin-dependent kinase 5 in the neuroprotective properties of lithium. Jordà, E.G., Verdaguer, E., Canudas, A.M., Jiménez, A., Garcia de Arriba, S., Allgaier, C., Pallàs, M., Camins, A. Neuroscience (2005) [Pubmed]
  16. Outer dense fibers serve as a functional target for Cdk5.p35 in the developing sperm tail. Rosales, J.L., Lee, B.C., Modarressi, M., Sarker, K.P., Lee, K.Y., Jeong, Y.G., Oko, R., Lee, K.Y. J. Biol. Chem. (2004) [Pubmed]
  17. Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau. Zhu, D., Kosik, K.S., Meigs, T.E., Yanamadala, V., Denker, B.M. J. Biol. Chem. (2004) [Pubmed]
  18. Activation of cyclin-dependent kinase 5 is involved in axonal regeneration. Namgung, U., Choi, B.H., Park, S., Lee, J.U., Seo, H.S., Suh, B.C., Kim, K.T. Mol. Cell. Neurosci. (2004) [Pubmed]
  19. Both N-methyl-D-aspartate (NMDA) and non-NMDA receptors mediate glutamate-induced cleavage of the cyclin-dependent kinase 5 (cdk5) activator p35 in cultured rat hippocampal neurons. Kerokoski, P., Suuronen, T., Salminen, A., Soininen, H., Pirttilä, T. Neurosci. Lett. (2004) [Pubmed]
  20. Activity and regulation of p35/Cdk5 kinase complex. Nikolic, M., Tsai, L.H. Meth. Enzymol. (2000) [Pubmed]
  21. Prolongation of rat intestinal allograft survival by administration of donor interleukin-12 p35-silenced bone marrow-derived dendritic cells. Xu, H., Chen, T., Wang, H.Q., Ji, M.J., Zhu, X., Wu, W.X. Transplant. Proc. (2006) [Pubmed]
  22. Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25. Kusakawa, G., Saito, T., Onuki, R., Ishiguro, K., Kishimoto, T., Hisanaga, S. J. Biol. Chem. (2000) [Pubmed]
  23. Region-specific expression of cyclin-dependent kinase 5 (cdk5) and its activators, p35 and p39, in the developing and adult rat central nervous system. Zheng, M., Leung, C.L., Liem, R.K. J. Neurobiol. (1998) [Pubmed]
  24. Induction of Cdk5 activity in rat skeletal muscle after nerve injury. Fu, W.Y., Fu, A.K., Lok, K.C., Ip, F.C., Ip, N.Y. Neuroreport (2002) [Pubmed]
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