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Gene Review

CDC2L2  -  cell division cycle 2-like 2 (PITSLRE...

Homo sapiens

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Disease relevance of CDC2L2


High impact information on CDC2L2

  • Our data suggest the existence of an IRES-dependent cascade in mitosis comprising hnRNP C1/C2 proteins that stimulate Unr expression, and Unr, in turn, contributes to PITSLRE IRES activity [4].
  • For example, the Unr protein contributes to translation mediated by several viral and cellular internal ribosome entry sites (IRESs), including the PITSLRE IRES, which is activated at mitosis [4].
  • PITSLRE protein kinase activity is associated with apoptosis [5].
  • To test this hypothesis, we examined levels of PITSLRE mRNA, steady-state protein, and enzyme activity in human T cells undergoing apoptosis after activation with the anti-Fas monoclonal antibody (MAb) [5].
  • Minimal ectopic expression of a 58-kDa protein kinase (PITSLRE beta 1), distantly related to members of the cdc2 gene family, induces telophase delay, abnormal chromosome segregation, and decreased growth rates in Chinese hamster ovary cells [5].

Biological context of CDC2L2


Anatomical context of CDC2L2

  • TNF-induced proteolysis of PITSLRE kinases was still observed in fibroblasts from CASP-1(0/0) mice [6].
  • Transient expression of the p58GTA protein kinase, which belongs to the p34cdc2-related supergene family, could enhance beta1,4-GT 1 total activity in COS cells [7].
  • Here we show that multiple caspase-like activities are involved in the processing of the PITSLRE p110 isoforms during Fas-induced apoptosis in Jurkat T-cells [8].
  • Finally, we demonstrate that the PITSLRE p110 protein is rapidly phosphorylated during Fas-induced apoptosis in Jurkat cells and that phosphorylation of an amino-terminal portion of the protein may enhance caspase cleavage in this region [8].
  • The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation [9].

Associations of CDC2L2 with chemical compounds

  • These results suggest that the p58GTA stable transfection into human hepatocarcinoma cells could enhance the two beta1,4-GT1 subcellular pool activities independently and change its cell-cycle without modifying the beta-1,4-linked galactose residues on most membrane proteins [7].
  • In this study, the p58GTA interaction with beta1,4-GT 1 was confirmed using an in vitro assay with the TNT Coupled Reticulocyte Lysate System. An expression vector containing p58GTA was stably transfected into 7721 cells, a human hepatocarcinoma cell line, expression was confirmed by Northern and Western blot analyses [7].
  • Progressive deletion analysis showed that both a purine-rich sequence and a Unr (upstream of N-ras) consensus binding site are essential for PITSLRE IRES activity [3].
  • These findings suggest that (i) PITSLRE kinase(s) may lie within apoptotic signaling pathway(s), (ii) serine protease activation may be an early event in Fas-activated apoptosis of human T cells, and (iii) some PITSLRE kinase isoforms may be targets of apoptotic proteases [5].
  • Furthermore, 2-aminopurine inhibits PITSLRE beta 1 protein kinase activity in vivo, but does not effect p34cdc2 protein kinase activity in a similar manner [10].

Physical interactions of CDC2L2

  • These data indicate that the PITSLRE p110 isoforms interact with RNPS1 in vivo, and that these proteins may in turn influence some aspect of transcriptional and/or splicing regulation [11].
  • We demonstrate that PITSLRE p110 protein kinases co-immunoprecipitate and/or co-purify with these elongation factors as well as with RNA polymerase II [12].

Other interactions of CDC2L2


Analytical, diagnostic and therapeutic context of CDC2L2


  1. Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma. Nelson, M.A., Ariza, M.E., Yang, J.M., Thompson, F.H., Taetle, R., Trent, J.M., Wymer, J., Massey-Brown, K., Broome-Powell, M., Easton, J., Lahti, J.M., Kidd, V.J. Cancer Genet. Cytogenet. (1999) [Pubmed]
  2. Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. Lahti, J.M., Valentine, M., Xiang, J., Jones, B., Amann, J., Grenet, J., Richmond, G., Look, A.T., Kidd, V.J. Nat. Genet. (1994) [Pubmed]
  3. Regulation of the cell-cycle-dependent internal ribosome entry site of the PITSLRE protein kinase: roles of Unr (upstream of N-ras) protein and phosphorylated translation initiation factor eIF-2alpha. Tinton, S.A., Schepens, B., Bruynooghe, Y., Beyaert, R., Cornelis, S. Biochem. J. (2005) [Pubmed]
  4. A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis. Schepens, B., Tinton, S.A., Bruynooghe, Y., Parthoens, E., Haegman, M., Beyaert, R., Cornelis, S. EMBO J. (2007) [Pubmed]
  5. PITSLRE protein kinase activity is associated with apoptosis. Lahti, J.M., Xiang, J., Heath, L.S., Campana, D., Kidd, V.J. Mol. Cell. Biol. (1995) [Pubmed]
  6. Cleavage of PITSLRE kinases by ICE/CASP-1 and CPP32/CASP-3 during apoptosis induced by tumor necrosis factor. Beyaert, R., Kidd, V.J., Cornelis, S., Van de Craen, M., Denecker, G., Lahti, J.M., Gururajan, R., Vandenabeele, P., Fiers, W. J. Biol. Chem. (1997) [Pubmed]
  7. Effect of p58GTA on beta-1,4-galactosyltransferase 1 activity and cell-cycle in human hepatocarcinoma cells. Zhang, S.W., Xu, S.L., Cai, M.M., Yan, J., Zhu, X.Y., Hu, Y., Gu, J.X. Mol. Cell. Biochem. (2001) [Pubmed]
  8. Phosphorylation of PITSLRE p110 isoforms accompanies their processing by caspases during Fas-mediated cell death. Tang, D., Gururajan, R., Kidd, V.J. J. Biol. Chem. (1998) [Pubmed]
  9. The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation. Petretti, C., Savoian, M., Montembault, E., Glover, D.M., Prigent, C., Giet, R. EMBO Rep. (2006) [Pubmed]
  10. 2-Aminopurine overrides a late telophase delay created by ectopic expression of the PITSLRE beta 1 protein kinase. Xiang, J., Lahti, J.M., Kidd, V.J. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  11. The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo. Loyer, P., Trembley, J.H., Lahti, J.M., Kidd, V.J. J. Cell. Sci. (1998) [Pubmed]
  12. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. Trembley, J.H., Hu, D., Hsu, L.C., Yeung, C.Y., Slaughter, C., Lahti, J.M., Kidd, V.J. J. Biol. Chem. (2002) [Pubmed]
  13. Regulation of stability of cyclin-dependent kinase CDK11p110 and a caspase-processed form, CDK11p46, by Hsp90. Mikolajczyk, M., Nelson, M.A. Biochem. J. (2004) [Pubmed]
  14. 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. 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. J. Biol. Chem. (2003) [Pubmed]
  15. The cyclin-dependent kinase 11 interacts with NOT2. Shi, J., Nelson, M.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. Molecular cloning and expression of alternatively spliced PITSLRE protein kinase isoforms. Xiang, J., Lahti, J.M., Grenet, J., Easton, J., Kidd, V.J. J. Biol. Chem. (1994) [Pubmed]
  17. Fas-induced apoptosis in human malignant melanoma cell lines is associated with the activation of the p34(cdc2)-related PITSLRE protein kinases. Ariza, M.E., Broome-Powell, M., Lahti, J.M., Kidd, V.J., Nelson, M.A. J. Biol. Chem. (1999) [Pubmed]
  18. Induction of differentiation and c-jun expression in human leukemic cells by okadaic acid, an inhibitor of protein phosphatases. Adunyah, S.E., Unlap, T.M., Franklin, C.C., Kraft, A.S. J. Cell. Physiol. (1992) [Pubmed]
  19. Structure and expression of chicken protein kinase PITSLRE-encoding genes. Li, H., Grenet, J., Valentine, M., Lahti, J.M., Kidd, V.J. Gene (1995) [Pubmed]
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