Display options
Cite
Megyesi J, Tarcsafalvi A, Seng N, et al. Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak. Cell Death Discov. 2016;2doi: 10.1038/cddiscovery.2015.66.
Megyesi, J., Tarcsafalvi, A., Seng, N., Hodeify, R., & Price, P. M. (2016). Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak. Cell death discovery, 2. https://doi.org/10.1038/cddiscovery.2015.66
Megyesi, J, et al. "Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak." Cell death discovery vol. 2 (2016). doi: https://doi.org/10.1038/cddiscovery.2015.66
Megyesi J, Tarcsafalvi A, Seng N, Hodeify R, Price PM. Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak. Cell Death Discov. 2016;2. doi: 10.1038/cddiscovery.2015.66. Epub 2016 Jan 18. PMID: 27226901; PMCID: PMC4877050.
Copy Download .nbib Format: NLM
Share it on

Cell Death Discov. 2016;2. doi: 10.1038/cddiscovery.2015.66. Epub 2016 Jan 18.

Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak.

Cell death discovery

J Megyesi, A Tarcsafalvi, Nshl Seng, R Hodeify, P M Price

Affiliations

  1. Department of Internal Medicine, Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
  2. Department of Internal Medicine, Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
  3. Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
  4. Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.

PMID: 27226901 PMCID: PMC4877050 DOI: 10.1038/cddiscovery.2015.66

Abstract

Apoptosis is a regulated form of cell death that proceeds by defined biochemical pathways. Most apoptosis is controlled by interactions between pro-survival and pro-apoptotic Bcl-2 family proteins in which death is often the consequence of permeabilization of the mitochondrial outer membrane. Many drugs affect this equilibrium to favor apoptosis but this process is not completely understood. We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. The phosphorylation occurred at a previously unreported site and its biologic significance was demonstrated by a phosphomimetic modification of Bcl-xL that was able to induce apoptosis without addition of cisplatin. The mechanism of cell death induction was similar to that initiated by pro-apoptotic Bcl-2 family proteins, that is, phosphorylated Bcl-xL translocated to the mitochondrial membrane, and formed pores in the membrane. This initiated cytochrome

References

  1. Nat Rev Cancer. 2007 Aug;7(8):573-84 - PubMed
  2. Cell. 1996 Jul 12;86(1):147-57 - PubMed
  3. Curr Opin Pharmacol. 2015 Aug;23:74-81 - PubMed
  4. Nature. 1970 Aug 15;227(5259):680-5 - PubMed
  5. Am J Physiol Renal Physiol. 2004 Feb;286(2):F378-84 - PubMed
  6. Nature. 1992 May 21;357(6375):216-22 - PubMed
  7. Kidney Int. 2007 Jul;72(1):53-62 - PubMed
  8. J Cell Biol. 1999 Mar 8;144(5):891-901 - PubMed
  9. Kidney Int. 2008 May;73(9):994-1007 - PubMed
  10. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3668-72 - PubMed
  11. Am J Physiol. 1995 Aug;269(2 Pt 1):C323-33 - PubMed
  12. Cancer Cell. 2002 Sep;2(3):183-92 - PubMed
  13. Cell. 2000 Nov 10;103(4):645-54 - PubMed
  14. Am J Physiol Renal Physiol. 2005 Sep;289(3):F514-20 - PubMed
  15. Methods Cell Biol. 1994;41:15-38 - PubMed
  16. J Mol Biol. 2015 Jul 3;427(13):2257-61 - PubMed
  17. Nat Rev Drug Discov. 2005 Apr;4(4):307-20 - PubMed
  18. Mol Cell Biol. 2010 Feb;30(3):640-56 - PubMed
  19. FEBS Lett. 2003 Mar 13;538(1-3):41-7 - PubMed
  20. Biophys J. 2013 Jan 22;104(2):421-31 - PubMed
  21. Cell. 1990 May 18;61(4):549-51 - PubMed
  22. Mol Cell. 2005 Feb 4;17 (3):393-403 - PubMed
  23. J Biol Chem. 2008 Dec 19;283(51):35517-25 - PubMed
  24. Nat Rev Mol Cell Biol. 2001 Jan;2(1):63-7 - PubMed
  25. J Bioenerg Biomembr. 2009 Feb;41(1):29-40 - PubMed
  26. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766-70 - PubMed
  27. Curr Opin Cell Biol. 1999 Dec;11(6):745-52 - PubMed
  28. Structure. 2015 Jan 6;23(1):139-48 - PubMed
  29. EMBO J. 1993 May;12(5):1947-54 - PubMed
  30. Mol Cell. 2009 Nov 13;36(3):487-99 - PubMed
  31. Nature. 1995 Jul 6;376(6535):88-91 - PubMed
  32. Cell. 2009 Sep 4;138(5):838-54 - PubMed
  33. Mol Cell. 2008 May 9;30(3):369-80 - PubMed
  34. J Cell Biol. 2001 Jun 11;153(6):1265-76 - PubMed
  35. Mol Cell. 2010 Nov 12;40(3):481-92 - PubMed
  36. Nature. 1997 Jan 23;385(6614):353-7 - PubMed
  37. Cell. 1998 Jun 26;93(7):1147-58 - PubMed
  38. J Biol Chem. 1998 Apr 24;273(17 ):10777-83 - PubMed
  39. Cell. 1998 Aug 21;94(4):491-501 - PubMed
  40. Nat Cell Biol. 2000 Nov;2(11):819-25 - PubMed
  41. Mol Cell. 2011 Nov 18;44(4):517-31 - PubMed
  42. J Biol Chem. 2006 Jul 28;281(30):21353-61 - PubMed
  43. EMBO J. 1996 Feb 15;15(4):850-60 - PubMed
  44. Cell Death Dis. 2014 Jun 12;5:e1291 - PubMed
  45. Cell Death Differ. 2013 Jul;20(7):920-30 - PubMed
  46. Mol Cell. 2013 Mar 7;49(5):959-71 - PubMed
  47. Mol Cell. 2005 Feb 18;17 (4):525-35 - PubMed
  48. Exp Cell Res. 1999 Nov 1;252(2):332-41 - PubMed
  49. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14 - PubMed
  50. Kidney Int. 2009 Sep;76(6):604-13 - PubMed
  51. Am J Physiol Renal Physiol. 2011 May;300(5):F1171-9 - PubMed
  52. Mol Cell Biol. 2001 Aug;21(15):4929-37 - PubMed
  53. Mol Cell Biol. 2000 Feb;20(3):929-35 - PubMed
  54. Cancer Res. 2013 Dec 1;73(23 ):6998-7008 - PubMed
  55. Nature. 1996 May 23;381(6580):335-41 - PubMed
  56. Science. 2007 Feb 9;315 (5813):856-9 - PubMed
  57. Oncogene. 2005 Jan 6;24(1):107-17 - PubMed
  58. Cell. 2013 Jan 31;152(3):519-31 - PubMed
  59. Nature. 2008 Oct 23;455(7216):1076-81 - PubMed
  60. J Clin Invest. 1999 Mar;103(5):597-604 - PubMed
  61. Oncogene. 2008 Jul 10;27(30):4221-32 - PubMed
  62. Am J Physiol Renal Physiol. 2008 Jul;295(1):F44-52 - PubMed
  63. Nat Cell Biol. 2000 Mar;2(3):156-62 - PubMed
  64. Mol Cell Biol. 1998 May;18(5):2912-22 - PubMed
  65. Trends Genet. 1996 Sep;12(9):345-50 - PubMed
  66. J Am Soc Nephrol. 2006 Sep;17(9):2434-42 - PubMed
  67. Cancer Lett. 2005 Jan 20;217(2):129-38 - PubMed
  68. Nat Rev Mol Cell Biol. 2008 Nov;9(11):910-6 - PubMed
  69. Curr Biol. 1994 Nov 1;4(11):973-82 - PubMed
  70. Oncogene. 2009 Aug 20;28(33):2925-39 - PubMed
  71. J Mol Biol. 2015 Jul 3;427(13):2262-70 - PubMed
  72. J Immunol. 2000 Nov 15;165(10):5612-20 - PubMed
  73. Mol Cell. 2014 Nov 20;56(4):496-505 - PubMed
  74. J Biol Chem. 1999 Nov 5;274(45):31775-83 - PubMed
  75. Cell. 1993 Aug 27;74(4):609-19 - PubMed
  76. J Cell Physiol. 2011 Feb;226(2):341-9 - PubMed
  77. Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59 - PubMed

Publication Types

Grant support