#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The actin nucleation factors JMY and WHAMM enable a rapid Arp2/3 complex-mediated intrinsic pathway of apoptosis


Autoři: Virginia L. King aff001;  Nathan K. Leclair aff001;  Alyssa M. Coulter aff001;  Kenneth G. Campellone aff001
Působiště autorů: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, United States of America aff001
Vyšlo v časopise: The actin nucleation factors JMY and WHAMM enable a rapid Arp2/3 complex-mediated intrinsic pathway of apoptosis. PLoS Genet 17(4): e1009512. doi:10.1371/journal.pgen.1009512
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009512

Souhrn

The actin cytoskeleton is a well-known player in most vital cellular processes, but comparably little is understood about how the actin assembly machinery impacts programmed cell death pathways. In the current study, we explored roles for the human Wiskott-Aldrich Syndrome Protein (WASP) family of actin nucleation factors in DNA damage-induced apoptosis. Inactivation of each WASP-family gene revealed that two of them, JMY and WHAMM, are necessary for rapid apoptotic responses. JMY and WHAMM participate in a p53-dependent cell death pathway by enhancing mitochondrial permeabilization, initiator caspase cleavage, and executioner caspase activation. JMY-mediated apoptosis requires actin nucleation via the Arp2/3 complex, and actin filaments are assembled in cytoplasmic territories containing clusters of cytochrome c and active caspase-3. The loss of JMY additionally results in significant changes in gene expression, including upregulation of the WHAMM-interacting G-protein RhoD. Depletion or deletion of RHOD increases cell death, suggesting that RhoD normally contributes to cell survival. These results give rise to a model in which JMY and WHAMM promote intrinsic cell death responses that can be opposed by RhoD.

Klíčová slova:

Apoptosis – Mitochondria – Actins – Antibody therapy – Cell staining – DAPI staining – DNA damage – Small interfering RNA


Zdroje

1. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–57. doi: 10.1038/bjc.1972.33 4561027

2. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3):486–541. doi: 10.1038/s41418-017-0012-4 29362479

3. Dickens LS, Powley IR, Hughes MA, MacFarlane M. The ’complexities’ of life and death: death receptor signalling platforms. Exp Cell Res. 2012;318(11):1269–77. doi: 10.1016/j.yexcr.2012.04.005 22542855

4. Tait SWG, Green DR. Mitochondrial regulation of cell death. Cold Spring Harb Perspect Biol. 2013;5(9): a008706. doi: 10.1101/cshperspect.a008706 24003207

5. von Karstedt S, Montinaro A, Walczak H. Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat Rev Cancer. 2017;17(6):352–66. doi: 10.1038/nrc.2017.28 28536452

6. Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019;20(3):175–93. doi: 10.1038/s41580-018-0089-8 30655609

7. Gourlay CW, Ayscough KR. The actin cytoskeleton: a key regulator of apoptosis and ageing? Nat Rev Mol Cell Biol. 2005;6(7):583–9. doi: 10.1038/nrm1682 16072039

8. Desouza M, Gunning PW, Stehn JR. The actin cytoskeleton as a sensor and mediator of apoptosis. Bioarchitecture. 2012;2(3):75–87. doi: 10.4161/bioa.20975 22880146

9. Campellone KG, Welch MD. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol. 2010;11(4):237–51. doi: 10.1038/nrm2867 20237478

10. Rottner K, Faix J, Bogdan S, Linder S, Kerkhoff E. Actin assembly mechanisms at a glance. J Cell Sci. 2017;130(20):3427–35. doi: 10.1242/jcs.206433 29032357

11. Pollard TD, Blanchoin L, Mullins RD. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol Struct. 2000;29: 545–76. doi: 10.1146/annurev.biophys.29.1.545 10940259

12. Rotty JD, Wu C, Bear JE. New insights into the regulation and cellular functions of the ARP2/3 complex. Nat Rev Mol Cell Biol. 2013;14(1):7–12. doi: 10.1038/nrm3492 23212475

13. Alekhina O, Burstein E, Billadeau DD. Cellular functions of WASP family proteins at a glance. J Cell Sci. 2017;130(14):2235–41. doi: 10.1242/jcs.199570 28646090

14. Kabrawala S, Zimmer MD, Campellone KG. WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility. PLoS Genet. 2020;16(3): e1008694. doi: 10.1371/journal.pgen.1008694 32196488

15. Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev Cell. 2009;17(5):712–23. doi: 10.1016/j.devcel.2009.09.010 19922875

16. Jia D, Gomez TS, Metlagel Z, Umetani J, Otwinowski Z, Rosen MK, et al. WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes. Proc Natl Acad Sci U S A. 2010;107(23):10442–7. doi: 10.1073/pnas.0913293107 20498093

17. Schnoor M, Stradal TE, Rottner K. Cortactin: Cell Functions of A Multifaceted Actin-Binding Protein. Trends Cell Biol. 2018;28(2):79–98. doi: 10.1016/j.tcb.2017.10.009 29162307

18. Kale J, Osterlund EJ, Andrews DW. BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ. 2018;25(1):65–80. doi: 10.1038/cdd.2017.186 29149100

19. Opferman JT, Kothari A. Anti-apoptotic BCL-2 family members in development. Cell Death Differ. 2018;25(1):37–45. doi: 10.1038/cdd.2017.170 29099482

20. Danial NN, Gramm CF, Scorrano L, Zhang C-Y, Krauss S, Ranger AM, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature. 2003;424(6951):952–6. doi: 10.1038/nature01825 12931191

21. Cheng A, Arumugam TV, Liu D, Khatri RG, Mustafa K, Kwak S, et al. Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death. J Neurosci. 2007;27(7):1519–28. doi: 10.1523/JNEUROSCI.5154-06.2007 17301160

22. Kang R, Tang D, Yu Y, Wang Z, Hu T, Wang H, et al. WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia. 2010;24(1):177–86. doi: 10.1038/leu.2009.224 19890377

23. Zhang Z, Wu B, Chai W, Cao L, Wang Y, Yu Y, et al. Knockdown of WAVE1 enhances apoptosis of leukemia cells by downregulating autophagy. Int J Oncol. 2016;48(6):2647–56. doi: 10.3892/ijo.2016.3446 27035872

24. Shikama N, Lee CW, France S, Delavaine L, Lyon J, Krstic-Demonacos M, et al. A novel cofactor for p300 that regulates the p53 response. Mol Cell. 1999;4(3):365–76. doi: 10.1016/s1097-2765(00)80338-x 10518217

25. Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell. 2017;170(6):1062–78. doi: 10.1016/j.cell.2017.08.028 28886379

26. Hafner A, Bulyk ML, Jambhekar A, Lahav G. The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol. 2019;20(4):199–210. doi: 10.1038/s41580-019-0110-x 30824861

27. Coutts AS, Boulahbel H, Graham A, La Thangue NB. Mdm2 targets the p53 transcription cofactor JMY for degradation. EMBO Rep. 2007;8(1):84–90. doi: 10.1038/sj.embor.7400855 17170761

28. Hu X, Mullins RD. LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation. J Cell Biol. 2019;218(1):251–66. doi: 10.1083/jcb.201802157 30420355

29. Coutts AS, Weston L, La Thangue NB. A transcription co-factor integrates cell adhesion and motility with the p53 response. Proc Natl Acad Sci U S A. 2009;106(47):19872–7. doi: 10.1073/pnas.0906785106 19897726

30. Zuchero JB, Belin B, Mullins RD. Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY. Mol Biol Cell. 2012;23(5):853–63. doi: 10.1091/mbc.E11-12-0992 22262458

31. Demonacos C, Krstic-Demonacos M, La Thangue NB. A TPR motif cofactor contributes to p300 activity in the p53 response. Mol Cell. 2001;8(1):71–84. doi: 10.1016/s1097-2765(01)00277-5 11511361

32. Coutts AS, La Thangue NB. Actin nucleation by WH2 domains at the autophagosome. Nat Commun. 2015;6: 7888–. doi: 10.1038/ncomms8888 26223951

33. Kotecki M, Reddy PS, Cochran BH. Isolation and characterization of a near-haploid human cell line. Exp Cell Res. 1999;252(2):273–80. doi: 10.1006/excr.1999.4656 10527618

34. Andersson BS, Collins VP, Kurzrock R, Larkin DW, Childs C, Ost A, et al. KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR transcripts. Leukemia. 1995;9(12):2100–8. 8609723

35. Essletzbichler P, Konopka T, Santoro F, Chen D, Gapp BV, Kralovics R, et al. Megabase-scale deletion using CRISPR/Cas9 to generate a fully haploid human cell line. Genome Res. 2014;24(12):2059–65. doi: 10.1101/gr.177220.114 25373145

36. Olbrich T, Mayor-Ruiz C, Vega-Sendino M, Gomez C, Ortega S, Ruiz S, et al. A p53-dependent response limits the viability of mammalian haploid cells. Proc Natl Acad Sci U S A. 2017;114(35):9367–72. doi: 10.1073/pnas.1705133114 28808015

37. Campellone KG, Webb NJ, Znameroski EA, Welch MD. WHAMM is an Arp2/3 complex activator that binds microtubules and functions in ER to Golgi transport. Cell. 2008;134(1):148–61. doi: 10.1016/j.cell.2008.05.032 18614018

38. Dorstyn L, Akey CW, Kumar S. New insights into apoptosome structure and function. Cell Death Differ. 2018;25(7):1194–208. doi: 10.1038/s41418-017-0025-z 29765111

39. Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 2020;21(2):85–100. doi: 10.1038/s41580-019-0173-8 31636403

40. Green DR, Llambi F. Cell Death Signaling. Cold Spring Harb Perspect Biol. 2015;7(12): a006080. doi: 10.1101/cshperspect.a006080 26626938

41. Julien O, Wells JA. Caspases and their substrates. Cell Death Differ. 2017;24(8):1380–9. doi: 10.1038/cdd.2017.44 28498362

42. Andrysik Z, Galbraith MD, Guarnieri AL, Zaccara S, Sullivan KD, Pandey A, et al. Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity. Genome Res. 2017;27(10):1645–57. doi: 10.1101/gr.220533.117 28904012

43. Sullivan KD, Galbraith MD, Andrysik Z, Espinosa JM. Mechanisms of transcriptional regulation by p53. Cell Death Differ. 2018;25(1):133–43. doi: 10.1038/cdd.2017.174 29125602

44. Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 2009;9(6):400–14. doi: 10.1038/nrc2657 19440234

45. Gad AKB, Nehru V, Ruusala A, Aspenström P. RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting factor WASp homologue associated with actin Golgi membranes and microtubules. Mol Biol Cell. 2012;23(24):4807–19. doi: 10.1091/mbc.E12-07-0555 23087206

46. Blom M, Reis K, Nehru V, Blom H, Gad AK, Aspenström P. RhoD is a Golgi component with a role in anterograde protein transport from the ER to the plasma membrane. Exp Cell Res. 2015;333(2):208–19. doi: 10.1016/j.yexcr.2015.02.023 25746724

47. Russo AJ, Mathiowetz AJ, Hong S, Welch MD, Campellone KG. Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation. Mol Biol Cell. 2016;27(6):967–78. doi: 10.1091/mbc.E15-07-0508 26823012

48. Murphy C, Saffrich R, Grummt M, Gournier H, Rybin V, Rubino M, et al. Endosome dynamics regulated by a Rho protein. Nature. 1996;384(6608):427–32. doi: 10.1038/384427a0 8945468

49. Tsubakimoto K, Matsumoto K, Abe H, Ishii J, Amano M, Kaibuchi K, et al. Small GTPase RhoD suppresses cell migration and cytokinesis. Oncogene. 1999;18(15):2431–40. doi: 10.1038/sj.onc.1202604 10229194

50. Murphy C, Saffrich R, Olivo-Marin JC, Giner A, Ansorge W, Fotsis T, et al. Dual function of rhoD in vesicular movement and cell motility. Eur J Cell Biol. 2001;80(6):391–8. doi: 10.1078/0171-9335-00173 11484930

51. Aspenström P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem J. 2004;377(Pt 2):327–37. doi: 10.1042/BJ20031041 14521508

52. Koizumi K, Takano K, Kaneyasu A, Watanabe-Takano H, Tokuda E, Abe T, et al. RhoD activated by fibroblast growth factor induces cytoneme-like cellular protrusions through mDia3C. Mol Biol Cell. 2012;23(23):4647–61. doi: 10.1091/mbc.E12-04-0315 23034183

53. Nehru V, Voytyuk O, Lennartsson J, Aspenström P. RhoD binds the Rab5 effector Rabankyrin-5 and has a role in trafficking of the platelet-derived growth factor receptor. Traffic. 2013;14(12):1242–54. doi: 10.1111/tra.12121 24102721

54. Aspenström P. Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking. Biol Chem. 2014;395(5):477–84. doi: 10.1515/hsz-2013-0296 24622787

55. Blom M, Reis K, Heldin J, Kreuger J, Aspenström P. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration. Exp Cell Res. 2017;352(2):255–64. doi: 10.1016/j.yexcr.2017.02.013 28196728

56. Durkin CH, Leite F, Cordeiro JV, Handa Y, Arakawa Y, Valderrama F, et al. RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6. Dev Cell. 2017;41(3):315–29. e7. doi: 10.1016/j.devcel.2017.04.010 28486133

57. Kyrkou A, Soufi M, Bahtz R, Ferguson C, Bai M, Parton RG, et al. RhoD participates in the regulation of cell-cycle progression and centrosome duplication. Oncogene. 2013;32(14):1831–42. doi: 10.1038/onc.2012.195 22665057

58. Sadok A, Marshall CJ. Rho GTPases: masters of cell migration. Small GTPases. 2014;5: e29710. doi: 10.4161/sgtp.29710 24978113

59. Ridley AJ. Rho GTPase signalling in cell migration. Curr Opin Cell Biol. 2015;36: 103–12. doi: 10.1016/j.ceb.2015.08.005 26363959

60. Zuchero JB, Coutts AS, Quinlan ME, Thangue NBL, Mullins RD. p53-cofactor JMY is a multifunctional actin nucleation factor. Nat Cell Biol. 2009;11(4):451–9. doi: 10.1038/ncb1852 19287377

61. Bratton SB, Salvesen GS. Regulation of the Apaf-1-caspase-9 apoptosome. J Cell Sci. 2010;123(Pt 19):3209–14. doi: 10.1242/jcs.073643 20844150

62. Yuan S, Akey CW. Apoptosome structure, assembly, and procaspase activation. Structure. 2013;21(4):501–15. doi: 10.1016/j.str.2013.02.024 23561633

63. Mashima T, Naito M, Fujita N, Noguchi K, Tsuruo T. Identification of actin as a substrate of ICE and an ICE-like protease and involvement of an ICE-like protease but not ICE in VP-16-induced apoptosis. Biochem Biophys Res Commun. 1995;217(3):1185–92. doi: 10.1006/bbrc.1995.2894 8554575

64. Mashima T, Naito M, Noguchi K, Miller DK, Nicholson DW, Tsuruo T. Actin cleavage by CPP-32/apopain during the development of apoptosis. Oncogene. 1997;14(9):1007–12. doi: 10.1038/sj.onc.1200919 9070648

65. Kayalar C, Ord T, Testa MP, Zhong LT, Bredesen DE. Cleavage of actin by interleukin 1 beta-converting enzyme to reverse DNase I inhibition. Proc Natl Acad Sci U S A. 1996;93(5):2234–8. doi: 10.1073/pnas.93.5.2234 8700913

66. Mashima T, Naito M, Tsuruo T. Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene. 1999;18(15):2423–30. doi: 10.1038/sj.onc.1202558 10229193

67. Utsumi T, Sakurai N, Nakano K, Ishisaka R. C-terminal 15 kDa fragment of cytoskeletal actin is posttranslationally N-myristoylated upon caspase-mediated cleavage and targeted to mitochondria. FEBS Lett. 2003;539(1–3):37–44. doi: 10.1016/s0014-5793(03)00180-7 12650923

68. Kanellos G, Frame MC. Cellular functions of the ADF/cofilin family at a glance. J Cell Sci. 2016;129(17):3211–8. doi: 10.1242/jcs.187849 27505888

69. Chua BT, Volbracht C, Tan KO, Li R, Yu VC, Li P. Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat Cell Biol. 2003;5(12):1083–9. doi: 10.1038/ncb1070 14634665

70. Zhu B, Fukada K, Zhu H, Kyprianou N. Prohibitin and cofilin are intracellular effectors of transforming growth factor beta signaling in human prostate cancer cells. Cancer Res. 2006;66(17):8640–7. doi: 10.1158/0008-5472.CAN-06-1443 16951178

71. Klamt F, Zdanov S, Levine RL, Pariser A, Zhang Y, Zhang B, et al. Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat Cell Biol. 2009;11: 1241–6. doi: 10.1038/ncb1968 19734890

72. Liu T, Wang F, LePochat P, Woo JA, Bukhari MZ, Hong KW, et al. Cofilin-mediated Neuronal Apoptosis via p53 Translocation and PLD1 Regulation. Sci Rep. 2017;7(1):11532. doi: 10.1038/s41598-017-09996-3 28912445

73. Tang HL, Le AH, Lung HL. The increase in mitochondrial association with actin precedes Bax translocation in apoptosis. Biochem J. 2006;396(1):1–5. doi: 10.1042/BJ20060241 16536728

74. Wang C, Zhou GL, Vedantam S, Li P, Field J. Mitochondrial shuttling of CAP1 promotes actin- and cofilin-dependent apoptosis. J Cell Sci. 2008;121(Pt 17):2913–20. doi: 10.1242/jcs.023911 18716285

75. Rehklau K, Gurniak CB, Conrad M, Friauf E, Ott M, Rust MB. ADF/cofilin proteins translocate to mitochondria during apoptosis but are not generally required for cell death signaling. Cell Death Differ. 2012;19(6):958–67. doi: 10.1038/cdd.2011.180 22139132

76. McGough AM, Staiger CJ, Min JK, Simonetti KD. The gelsolin family of actin regulatory proteins: modular structures, versatile functions. FEBS Lett. 2003;552(2–3):75–81. doi: 10.1016/s0014-5793(03)00932-3 14527663

77. Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, et al. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science. 1997;278(5336):294–8. doi: 10.1126/science.278.5336.294 9323209

78. Chhabra D, Nosworthy NJ, dos Remedios CG. The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex. Proteomics. 2005;5(12):3131–6. doi: 10.1002/pmic.200401127 16021605

79. Zuo W, Guo WS, Yu HC, Liu P, Zhang QD. Role of Junction-Mediating and Regulatory Protein in the Pathogenesis of Glucocorticoid-Induced Endothelial Cell Lesions. Orthop Surg. 2020. doi: 10.1111/os.12680 32363797

80. Schlüter K, Waschbüsch D, Anft M, Hügging D, Kind S, Hänisch J, et al. JMY is involved in anterograde vesicle trafficking from the trans-Golgi network. Eur J Cell Biol. 2014;93(5–6):194–204. doi: 10.1016/j.ejcb.2014.06.001 25015719

81. Kast DJ, Zajac AL, Holzbaur ELF, Ostap EM, Dominguez R. WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism. Curr Biol. 2015;25(13):1791–7. doi: 10.1016/j.cub.2015.05.042 26096974

82. Mathiowetz AJ, Baple E, Russo AJ, Coulter AM, Carrano E, Brown JD, et al. An Amish founder mutation disrupts a PI (3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway. Mol Biol Cell. 2017;28(19):2492–507. doi: 10.1091/mbc.E17-01-0022 28720660

83. Shen Q-T, Hsiue PP, Sindelar CV, Welch MD, Campellone KG, Wang H-W. Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling. J Cell Biol. 2012;199(1):111–24. doi: 10.1083/jcb.201204010 23027905

84. Dai A, Yu L, Wang HW. WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. Nat Commun. 2019;10(1):3699. doi: 10.1038/s41467-019-11694-9 31420534

85. Gu W, Roeder RG. Activation of p53 Sequence-Specific DNABinding by Acetylation of the p53 C-Terminal Domain. Cell. 1997;90(4):595–601. doi: 10.1016/s0092-8674(00)80521-8 9288740

86. Gu W, Shi XL, Roeder RG. Synergistic activation of transcription by CBP and p53. Nature. 1997;387(6635):819–23. doi: 10.1038/42972 9194564

87. Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, et al. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell. 2001;8(6):1243–54. doi: 10.1016/s1097-2765(01)00414-2 11779500

88. Erster S, Moll UM. Stress-induced p53 runs a transcription-independent death program. Biochem Biophys Res Commun. 2005;331(3):843–50. doi: 10.1016/j.bbrc.2005.03.187 15865940

89. Green DR, Kroemer G. Cytoplasmic functions of the tumour suppressor p53. Nature. 2009;458(7242):1127–30. doi: 10.1038/nature07986 19407794

90. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 2008;9(5):402–12. doi: 10.1038/nrm2395 18431400

91. Beckerman R, Prives C. Transcriptional regulation by p53. Cold Spring Harb Perspect Biol. 2010;2(8): a000935. doi: 10.1101/cshperspect.a000935 20679336

92. Zou H, Li Y, Liu X, Wang X. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem. 1999;274(17):11549–56. doi: 10.1074/jbc.274.17.11549 10206961

93. Nürnberg A, Kitzing T, Grosse R. Nucleating actin for invasion. Nat Rev Cancer. 2011;11(3):177–87. doi: 10.1038/nrc3003 21326322

94. Molinie N, Gautreau A. The Arp2/3 Regulatory System and Its Deregulation in Cancer. Physiol Rev. 2018;98(1):215–38. doi: 10.1152/physrev.00006.2017 29212790

95. Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017;17(9):528–42. doi: 10.1038/nrc.2017.53 28751651

96. Poillet-Perez L, White E. Role of tumor and host autophagy in cancer metabolism. Genes Dev. 2019;33(11–12):610–9. doi: 10.1101/gad.325514.119 31160394

97. Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1): a001008. doi: 10.1101/cshperspect.a001008 20182602

98. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9. doi: 10.1038/nature12634 24132290

99. Mantovani F, Collavin L, Del Sal G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ. 2019;26(2):199–212. doi: 10.1038/s41418-018-0246-9 30538286

100. Adighibe O, Turley H, Leek R, Harris A, Coutts AS, La Thangue N, et al. JMY protein, a regulator of P53 and cytoplasmic actin filaments, is expressed in normal and neoplastic tissues. Virchows Arch. 2014;465(6):715–22. doi: 10.1007/s00428-014-1660-0 25280461

101. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature. 2011;477(7364):340–3. doi: 10.1038/nature10348 21866103

102. Campellone KG, Leong JM. Nck-independent actin assembly is mediated by two phosphorylated tyrosines within enteropathogenic Escherichia coli Tir. Mol Microbiol. 2005;56(2):416–32. doi: 10.1111/j.1365-2958.2005.04558.x 15813734

103. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. doi: 10.1038/nmeth.2019 22743772


Článek vyšel v časopise

PLOS Genetics


2021 Číslo 4
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autoři: MUDr. Tomáš Ürge, PhD.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Závislosti moderní doby – digitální závislosti a hypnotika
Autoři: MUDr. Vladimír Kmoch

Aktuální možnosti diagnostiky a léčby AML a MDS nízkého rizika
Autoři: MUDr. Natália Podstavková

Jak diagnostikovat a efektivně léčit CHOPN v roce 2024
Autoři: doc. MUDr. Vladimír Koblížek, Ph.D.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#