Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Dongli HuEmail author
  • Jill M. Lahti
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_546


Historical Background

The CDK11A and CDK11B kinases (cyclin-dependent kinase 11A and B), formerly known as PITSLRE protein kinases, are serine/threonine protein kinases that belong to p34CDC2-related protein kinase superfamily. p34CDC2-related kinases play essential roles in many aspects of the cellular processes, especially cell cycle control and the regulation of transcription. There are two CDK11 genes in humans (CDK11A and CDK11B formerly known as CDC2L2 and CDC2L1), and one CDK11 gene in mouse (Cdk11, previously known as cdc2l) (Malumbres et al. 2009). CDK11 genes are evolutionarily conserved. CDK11 homologs are found in human, mouse, rat, frog, cattle, fruit fly, yeast, and even in protozoa amoeba (Trembley et al. 2004; Goldberg et al. 2006). The almost...

This is a preview of subscription content, log in to check access.


  1. Barna M, Pusic A, Zollo O, Costa M, Kondrashov N, Rego E, Rao PH, Ruggero D. Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature. 2008;456:971–5.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Beyaert R, Kidd VJ, Cornelis S, Van de Craen M, Denecker G, Lahti JM, Gururajan R, Vandenabeele P, Fiers W. Cleavage of PITSLRE kinases by ICE/CASP-1 and CPP32/CASP-3 during apoptosis induced by tumor necrosis factor. J Biol Chem. 1997;272:11694–7.PubMedCrossRefGoogle Scholar
  3. Bunnell BA, Heath LS, Adams DE, Lahti JM, Kidd VJ. Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle. Proc Natl Acad Sci U S A. 1990;87:7467–71.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chen S, Yin X, Zhu X, Yan J, Ji S, Chen C, Cai M, Zhang S, Zong H, Hu Y, Yuan Z, Shen Z, Gu J. The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis. J Biol Chem. 2003;278:20029–36.PubMedCrossRefGoogle Scholar
  5. Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006;127:469–80.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Cornelis S, Bruynooghe Y, Denecker G, Van Huffel S, Tinton S, Beyaert R. Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol Cell. 2000;5:597–605.PubMedCrossRefGoogle Scholar
  7. Chandramouli A, Shi J, Feng Y, Holubec H, Shanas RM, Bhattacharyya AK, Zheng W, Nelson MA. Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice. Carcinogenesis. 2007;28:2028–35.PubMedCrossRefGoogle Scholar
  8. Dickinson LA, Edgar AJ, Ehley J, Gottesfeld JM. Cyclin L is an RS domain protein involved in pre-mRNA splicing. J Biol Chem. 2002;277:25465–73.PubMedCrossRefGoogle Scholar
  9. Evangelista M, Lim TY, Lee J, Parker L, Ashique A, Peterson AS, Ye W, Davis DP, de Sauvage FJ. Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal transduction. Sci Signal. 2008;1(39):ra7.PubMedCrossRefGoogle Scholar
  10. Goldberg JM, Manning G, Liu A, Fey P, Pilcher KE, Xu Y, Smith JL. The dictyostelium kinome–analysis of the protein kinases from a simple model organism. PLoS Genet. 2006;2(3):e38.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Gururajan R, Lahti JM, Grenet J, Easton J, Gruber I, Ambros PF, Kidd VJ. Duplication of a genomic region containing the Cdc2L1-2 and MMP21-22 genes on human chromosome 1p36.3 and their linkage to D1Z2. Genome Res. 1998;8:929–39.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Hirose Y, Ohkuma Y. Phosphorylation of the C-terminal domain of RNA polymerase II plays central roles in the integrated events of eukaryotic gene expression. J Biochem. 2007;141:601–8.PubMedCrossRefGoogle Scholar
  13. Hu D, Mayeda A, Trembley JH, Lahti JM, Kidd VJ. CDK11 complexes promote pre-mRNA splicing. J Biol Chem. 2003;278:8623–9.PubMedCrossRefGoogle Scholar
  14. Hu D, Valentine M, Kidd VJ, Lahti JM. CDK11(p58) is required for the maintenance of sister chromatid cohesion. J Cell Sci. 2007;120:2424–34.PubMedCrossRefGoogle Scholar
  15. Lahti JM, Valentine M, Xiang J, Jones B, Amann J, Grenet J, Richmond G, Look AT, Kidd VJ. Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. Nat Genet. 1994;7:370–5.PubMedCrossRefGoogle Scholar
  16. Lahti JM, Xiang J, Heath LS, Campana D, Kidd VJ. PITSLRE protein kinase activity is associated with apoptosis. Mol Cell Biol. 1995;15:1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Li T, Inoue A, Lahti JM, Kidd VJ. Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Mol Cell Biol. 2004;24:3188–97.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Loyer P, Trembley JH, Lahti JM, Kidd VJ. The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo. J Cell Sci. 1998;111:1495–506.PubMedPubMedCentralGoogle Scholar
  19. Loyer P, Trembley JH, Grenet JA, Busson A, Corlu A, Zhao W, Kocak M, Kidd VJ, Lahti JM. Characterization of cyclin L1 and L2 interactions with CDK11 and splicing factors: influence of cyclin L isoforms on splice site selection. J Biol Chem. 2008;283:7721–32.PubMedCrossRefGoogle Scholar
  20. Malumbres M, Harlow E, Hunt T, Hunter T, Lahti JM, Manning G, Morgan DO, Tsai LH, Wolgemuth DJ. Cyclin-dependent kinases: a family portrait. Nat Cell Biol. 2009;11:1275–6.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Naik S, Dothager RS, Marasa J, Lewis CL, Piwnica-Worms D. Vascular endothelial growth factor receptor-1 is synthetic lethal to aberrant β-catenin activation in colon cancer. Clin Cancer Res. 2009;15:7529–37.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Pak V, Eifler TT, Jäger S, Krogan NJ, Fujinaga K, Peterlin BM. CDK11 in TREX/THOC regulates HIV mRNA 3′ end processing. Cell Host Microbe. 2015;18:560–70.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Petretti C, Savoian M, Montembault E, Glover DM, Prigent C, Giet R. The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation. EMBO Rep. 2006;7:418–24.PubMedPubMedCentralGoogle Scholar
  24. Shi J, Hershey JW, Nelson MA. Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis. FEBS Lett. 2009;583:971–7.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Shi L, Nishioka WK, Th’ng J, Bradbury EM, Litchfield DW, Greenberg AH. Premature p34cdc2 activation required for apoptosis. Science. 1994;263:1143–5.PubMedCrossRefGoogle Scholar
  26. Tang D, Gururajan R, Kidd VJ. Phosphorylation of PITSLRE p110 isoforms accompanies their processing by caspases during Fas-mediated cell death. J Biol Chem. 1998;273:16601–7.PubMedCrossRefGoogle Scholar
  27. Trembley JH, Hu D, Hsu LC, Yeung CY, Slaughter C, Lahti JM, Kidd VJ. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J Biol Chem. 2002;277:2589–96.PubMedCrossRefGoogle Scholar
  28. Trembley JH, Hu D, Slaughter CA, Lahti JM, Kidd VJ. Casein kinase 2 interacts with cyclin-dependent kinase 11 (CDK11) in vivo and phosphorylates both the RNA polymerase II carboxyl-terminal domain and CDK11 in vitro. J Biol Chem. 2003;278:2265–70.PubMedCrossRefGoogle Scholar
  29. Trembley JH, Loyer P, Hu D, Li T, Grenet J, Lahti JM, Kidd VJ. Cyclin dependent kinase 11 in RNA transcription and splicing. Prog Nucleic Acid Res Mol Biol. 2004;77:263–88.PubMedCrossRefGoogle Scholar
  30. Valente ST, Gilmartin GM, Venkatarama K, Arriagada G, Goff SP. HIV-1 mRNA 3′ end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8. Mol Cell. 2009;36:279–89.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Wilker EW, van Vugt MA, Artim SA, Huang PH, Petersen CP, Reinhardt HC, Feng Y, Sharp PA, Sonenberg N, White FM, Yaffe MB. 14-3-3sigma controls mitotic translation to facilitate cytokinesis. Nature. 2007;446:329–32.PubMedCrossRefGoogle Scholar
  32. Xiang J, Lahti JM, Grenet J, Easton J, Kidd VJ. Molecular cloning and expression of alternatively spliced PITSLRE protein kinase isoforms. J Biol Chem. 1994;269:15786–94.PubMedPubMedCentralGoogle Scholar
  33. Yokoyama H, Gruss OJ, Rybina S, Caudron M, Schelder M, Wilm M, Mattaj IW, Karsenti E. Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate. J Cell Biol. 2008;180:867–75.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Zhang Z, Yao R, Li J, Wang Y, Boone CW, Lubet RA, You M. Induction of invasive mouse skin carcinomas in transgenic mice with mutations in both H-ras and p53. Mol Cancer Res. 2005;3:563–74.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of SurgerySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of Tumor Cell BiologySt. Jude Children’s Research HospitalMemphisUSA