Display options
Cite
Celano SL, Yco LP, Kortus MG, et al. Identification of Kinases Responsible for p53-Dependent Autophagy. iScience. 2019;15:109-118doi: 10.1016/j.isci.2019.04.023.
Celano, S. L., Yco, L. P., Kortus, M. G., Solitro, A. R., Gunaydin, H., Scott, M., Spooner, E., O'Hagan, R. C., Fuller, P., Martin, K. R., Shumway, S. D., & MacKeigan, J. P. (2019). Identification of Kinases Responsible for p53-Dependent Autophagy. iScience, 15109-118. https://doi.org/10.1016/j.isci.2019.04.023
Celano, Stephanie L, et al. "Identification of Kinases Responsible for p53-Dependent Autophagy." iScience vol. 15 (2019): 109-118. doi: https://doi.org/10.1016/j.isci.2019.04.023
Celano SL, Yco LP, Kortus MG, Solitro AR, Gunaydin H, Scott M, Spooner E, O'Hagan RC, Fuller P, Martin KR, Shumway SD, MacKeigan JP. Identification of Kinases Responsible for p53-Dependent Autophagy. iScience. 2019 May 31;15:109-118. doi: 10.1016/j.isci.2019.04.023. Epub 2019 Apr 23. PMID: 31048145; PMCID: PMC6495467.
Copy Download .nbib Format: NLM
Share it on

iScience. 2019 May 31;15:109-118. doi: 10.1016/j.isci.2019.04.023. Epub 2019 Apr 23.

Identification of Kinases Responsible for p53-Dependent Autophagy.

iScience

Stephanie L Celano, Lisette P Yco, Matthew G Kortus, Abigail R Solitro, Hakan Gunaydin, Mark Scott, Edward Spooner, Ronan C O'Hagan, Peter Fuller, Katie R Martin, Stuart D Shumway, Jeffrey P MacKeigan

Affiliations

  1. College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Center for Cancer Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  2. College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
  3. Center for Cancer Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  4. Van Andel Institute Graduate School, Grand Rapids, MI 49503, USA.
  5. Department of Modeling & Informatics, Merck & Co., Inc., Boston, MA 02115, USA.
  6. Process Research & Development, Gilead Alberta ULC, Edmonton, AB T6S1A1, Canada.
  7. Department of Oncology, Merck & Co., Inc., Boston, MA 02115, USA.
  8. Discovery Chemistry, Merck & Co., Inc., Boston, MA 02115, USA.
  9. College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Center for Cancer Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA; Van Andel Institute Graduate School, Grand Rapids, MI 49503, USA. Electronic address: [email protected].

PMID: 31048145 PMCID: PMC6495467 DOI: 10.1016/j.isci.2019.04.023

Abstract

In cancer, autophagy is upregulated to promote cell survival and tumor growth during times of nutrient stress and can confer resistance to drug treatments. Several major signaling networks control autophagy induction, including the p53 tumor suppressor pathway. In response to DNA damage and other cellular stresses, p53 is stabilized and activated, while HDM2 binds to and ubiquitinates p53 for proteasome degradation. Thus blocking the HDM2-p53 interaction is a promising therapeutic strategy in cancer; however, the potential survival advantage conferred by autophagy induction may limit therapeutic efficacy. In this study, we leveraged an HDM2 inhibitor to identify kinases required for p53-dependent autophagy. Interestingly, we discovered that p53-dependent autophagy requires several kinases, including the myotonic dystrophy protein kinase-like alpha (MRCKα). MRCKα is a CDC42 effector reported to activate actin-myosin cytoskeletal reorganization. Overall, this study provides evidence linking MRCKα to autophagy and reveals additional insights into the role of kinases in p53-dependent autophagy.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: Biological Sciences; Cell Biology; Functional Aspects of Cell Biology

References

  1. J Biol Chem. 2001 Jun 22;276(25):23092-6 - PubMed
  2. Nat Rev Mol Cell Biol. 2003 Jun;4(6):446-56 - PubMed
  3. ACS Med Chem Lett. 2016 Jan 20;7(3):324-9 - PubMed
  4. Cancer Lett. 2015 Jun 1;361(2):185-96 - PubMed
  5. iScience. 2018 Oct 26;8:74-84 - PubMed
  6. Genes Dev. 2011 Mar 1;25(5):460-70 - PubMed
  7. Autophagy. 2016;12(1):1-222 - PubMed
  8. Nat Cell Biol. 2012 Aug;14(8):829-37 - PubMed
  9. Cell Signal. 2013 Jan;25(1):1-11 - PubMed
  10. PLoS One. 2011;6(9):e24825 - PubMed
  11. Nat Cell Biol. 2015 Sep;17(9):1112-23 - PubMed
  12. Nat Rev Cancer. 2009 Oct;9(10):749-58 - PubMed
  13. J Biol Chem. 2014 Sep 26;289(39):26989-7003 - PubMed
  14. Clin Cancer Res. 2011 Feb 15;17(4):654-66 - PubMed
  15. Nat Commun. 2013;4:2189 - PubMed
  16. Nat Rev Cancer. 2009 Nov;9(11):821-9 - PubMed
  17. Exp Cell Res. 1997 Jul 10;234(1):57-65 - PubMed
  18. Cell. 1992 Nov 13;71(4):587-97 - PubMed
  19. Nature. 2002 Jan 31;415(6871):530-6 - PubMed
  20. Nat Cell Biol. 2011 Feb;13(2):132-41 - PubMed
  21. J Clin Oncol. 2017 Apr 20;35(12):1304-1311 - PubMed
  22. Genes Cells. 2000 Jul;5(7):571-81 - PubMed
  23. Leuk Res. 2016 Sep;48:92-100 - PubMed
  24. Science. 2004 Feb 6;303(5659):844-8 - PubMed
  25. Oncogene. 2002 Feb 7;21(7):990-9 - PubMed
  26. Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364 - PubMed
  27. Cell. 2009 May 1;137(3):413-31 - PubMed
  28. Oncogene. 2002 Sep 5;21(39):6017-31 - PubMed
  29. J Hematol Oncol. 2017 Jul 3;10(1):133 - PubMed
  30. Biomolecules. 2018 Mar 21;8(2): - PubMed
  31. Nat Rev Cancer. 2003 Feb;3(2):102-9 - PubMed
  32. Nature. 1997 Oct 30;389(6654):990-4 - PubMed
  33. Cell. 2017 Sep 7;170(6):1062-1078 - PubMed
  34. Oncogene. 2000 Mar 30;19(14):1735-43 - PubMed
  35. Curr Biol. 2017 Apr 24;27(8):R318-R326 - PubMed
  36. Autophagy. 2008 Aug;4(6):810-4 - PubMed
  37. Mol Biol Cell. 2001 Dec;12(12):4013-29 - PubMed
  38. Nature. 1992 Jul 2;358(6381):15-6 - PubMed
  39. J Mol Med (Berl). 2014 Mar;92(3):217-25 - PubMed
  40. Mol Cancer Ther. 2005 Sep;4(9):1369-77 - PubMed
  41. Autophagy. 2014;10(12):2310-23 - PubMed
  42. Genes Dev. 2013 May 1;27(9):1016-31 - PubMed
  43. Cancer Res. 2004 Aug 1;64(15):5078-83 - PubMed
  44. Cell Death Differ. 2009 Jun;16(6):869-78 - PubMed
  45. Curr Biol. 2015 Jun 29;25(13):1791-7 - PubMed
  46. EMBO J. 2011 Feb 16;30(4):636-51 - PubMed
  47. Bioorg Med Chem Lett. 2014 Apr 15;24(8):1983-6 - PubMed
  48. Dev Cell. 2018 Mar 12;44(5):555-565.e3 - PubMed
  49. Cell Cycle. 2008 Oct;7(19):3006-11 - PubMed
  50. Nat Cell Biol. 2008 Jun;10(6):676-87 - PubMed
  51. Cell. 2008 Oct 3;135(1):123-36 - PubMed
  52. Genes Dev. 2011 Apr 1;25(7):717-29 - PubMed
  53. Cancer Res. 2018 Apr 15;78(8):2096-2114 - PubMed
  54. Cancer Biol Ther. 2017 Nov 2;18(11):895-903 - PubMed
  55. Cell. 1993 Nov 19;75(4):817-25 - PubMed
  56. Nat Cell Biol. 2005 Mar;7(3):255-61 - PubMed
  57. Genes Dev. 1993 Jul;7(7A):1126-32 - PubMed
  58. Cell Cycle. 2015;14(1):56-63 - PubMed
  59. Cell. 2017 Apr 6;169(2):361-371 - PubMed
  60. Oncogene. 1993 Dec;8(12):3411-6 - PubMed
  61. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14621-6 - PubMed
  62. Autophagy. 2015;11(9):1702-4 - PubMed
  63. Cell Commun Signal. 2014 Oct 05;12:54 - PubMed
  64. Nat Cell Biol. 2010 Jul;12(7):645-54 - PubMed
  65. J Biol Chem. 2001 Jun 15;276(24):21209-16 - PubMed
  66. Nat Rev Cancer. 2012 Apr 26;12(6):401-10 - PubMed
  67. Curr Opin Cell Biol. 2010 Apr;22(2):181-5 - PubMed
  68. J Biol Chem. 2006 Oct 20;281(42):31202-11 - PubMed
  69. Cell. 1995 Jan 27;80(2):293-9 - PubMed
  70. Cell. 2006 Jul 14;126(1):121-34 - PubMed
  71. Cancer Res. 1995 Jul 1;55(13):2910-9 - PubMed
  72. Nat Rev Cancer. 2014 May;14(5):359-70 - PubMed
  73. J Cell Biol. 2014 Aug 4;206(3):415-34 - PubMed
  74. Cell Struct Funct. 1998 Feb;23(1):33-42 - PubMed
  75. J Clin Invest. 2007 Feb;117(2):326-36 - PubMed
  76. Small GTPases. 2015;6(2):81-8 - PubMed

Publication Types

Grant support