The major isoforms of Bim contribute to distinct biological activities that govern the processes of autophagy and apoptosis in interleukin-7 dependent lymphocytes

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1823, Issue 10, 2012, Pages 1877-1893

  Ruppert, Shannon M ^a   Li, Wenqing ^b   Zhang, Ge ^a   Carlson, Adina L ^a   Limaye, Arati ^a   Durum, Scott K ^b   Khaled, Annette R ^a  

^a UNIVERSITY OF CENTRAL FLORIDA COLLEGE OF MEDICINE   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Acidification; Bcl 2; Cytokine; Dynein; Fluorescence; Lysosome

Indexed keywords

BIM PROTEIN; DYNEIN ADENOSINE TRIPHOSPHATASE; INTERLEUKIN 7; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 1; PROTEIN P62;

ACIDIFICATION; ANIMAL CELL; APOPTOSIS; ARTICLE; AUTOPHAGY; GENE OVEREXPRESSION; IMMUNOPRECIPITATION; LYSOSOME; NONHUMAN; PH; PRIORITY JOURNAL; T LYMPHOCYTE;

ACIDS; ADENINE; ANIMALS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; BCL-2-ASSOCIATED X PROTEIN; CELL PROLIFERATION; CYTOPLASMIC VESICLES; CYTOPROTECTION; DYNEINS; INTERLEUKIN-7; INTRACELLULAR SPACE; LYMPHOCYTES; LYSOSOMES; MEMBRANE PROTEINS; MICE; PROTEIN BINDING; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS;

EID: 84864554409     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2012.06.017     Document Type: Article

References (89)

1. Gross A., Mcdonnell J.M., Korsmeyer S.J. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 1999, 13:1899-1911.
2. Hildeman D.A., Zhu Y., Mitchell T.C., Bouillet P., Strasser A., Kappler J., Marrack P. Activated T cell death in vivo mediated by proapoptotic Bcl-2 family member Bim. Immunity 2002, 16:759-767.
3. Snow A.L., Oliveira J.B., Zheng L., Dale J.K., Fleisher T.A., Lenardo M.J. Critical role for Bim in T cell receptor restimulation-induced death. Biol. Direct 2008, 3:34.
4. Rathmell J.C., Vander Heiden M.G., Harris M.H., Frauwirth K.A., Thompson C.B. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol. Cell 2000, 6:683-692.
5. Sawa Y., Arima Y., Ogura H., Kitabayashi C., Jiang J.J., Fukushima T., Kamimura D., Hirano T., Murakami M. Hepatic interleukin-7 expression regulates T cell responses. Immunity 2009, 30:447-457.
6. Mazzucchelli R.I., Warming S., Lawrence S.M., Ishii M., Abshari M., Washington A.V., Feigenbaum L., Warner A.C., Sims D.J., Li W.Q., Hixon J.A., Gray D.H., Rich B.E., Morrow M., Anver M.R., Cherry J., Naf D., Sternberg L.R., Mcvicar D.W., Farr A.G., Germain R.N., Rogers K., Jenkins N.A., Copeland N.G., Durum S.K. Visualization and identification of IL-7 producing cells in reporter mice. PLoS One 2009, 4:E7637.
7. Kim G.Y., Hong C., Park J.H. Seeing is believing: illuminating the source of in vivo interleukin-7. Immune Netw. 2011, 11:1-10.
8. Jiang Q., Li W.Q., Aiello F.B., Mazzucchelli R., Asefa B., Khaled A.R., Durum S.K. Cell biology of IL-7, A key lymphotrophin. Cytokine Growth Factor Rev. 2005, 16:513-533.
9. Von-Freeden-Jeffry U., Vieira P., Lucian L.A., Mcneil T., Burdach S.E., Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 1995, 181:1519-1526.
10. Maraskovsky E., Teepe M., Morrissey P.J., Braddy S., Miller R.E., Lynch D.H., Peschon J.J. Impaired survival and proliferation in IL-7 receptor-deficient peripheral T cells. J. Immunol. 1996, 157:5315-5323.
11. Lai S.Y., Molden J., Goldsmith M.A. Shared gamma(C) subunit within the human interleukin-7 receptor complex. a molecular basis for the pathogenesis of X-linked severe combined immunodeficiency. J. Clin. Invest. 1997, 99:169-177.
12. Rich B.E., Campos-Torres J., Tepper R.I., Moreadith R.W., Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J. Exp. Med. 1993, 177:305-316.
13. Yamanaka K., Clark R., Rich B., Dowgiert R., Hirahara K., Hurwitz D., Shibata M., Mirchandani N., Jones D.A., Goddard D.S., Eapen S., Mizutani H., Kupper T.S. Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma. Blood 2006, 107:2440-2445.
14. Tan J.T., Dudl E., Leroy E., Murray R., Sprent J., Weinberg K.I., Surh C.D. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:8732-8737.
15. Maraskovsky E., Peschon J.J., Mckenna H., Teepe M., Strasser A. Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in IL-7 receptor-deficient mice but can enhance survival of mature B cells. Int. Immunol. 1998, 10:1367-1375.
16. Khaled A.R., Kim K., Hofmeister R., Muegge K., Durum S.K. Withdrawal of IL-7 induces Bax translocation from cytosol to mitochondria through a rise in intracellular pH. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:14476-14481.
17. Pellegrini M., Bouillet P., Robati M., Belz G.T., Davey G.M., Strasser A. Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J. Exp. Med. 2004, 200:1189-1195.
18. Puthalakath H., Huang D.C., O'reilly L.A., King S.M., Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 1999, 3:287-296.
19. Benison G., Karplus P.A., Barbar E. Structure and dynamics of LC8 complexes with KXTQT-motif peptides: swallow and dynein intermediate chain compete for a common site. J. Mol. Biol. 2007, 371:457-468.
20. Zhu Y., Swanson B.J., Wang M., Hildeman D.A., Schaefer B.C., Liu X., Suzuki H., Mihara K., Kappler J., Marrack P. Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:7681-7686.
21. Dijkers P.F., Birkenkamp K.U., Lam E.W., Thomas N.S., Lammers J.W., Koenderman L., Coffer P.J. Fkhr-L1 can act as a critical effector of cell death induced by cytokine withdrawal: protein kinase B-enhanced cell survival through maintenance of mitochondrial integrity. J. Cell Biol. 2002, 156:531-542.
22. Stahl M., Dijkers P.F., Kops G.J., Lens S.M., Coffer P.J., Burgering B.M., Medema R.H. The forkhead transcription factor Foxo regulates transcription of P27kip1 and Bim in response to IL-2. J. Immunol. 2002, 168:5024-5031.
23. Yano T., Ito K., Fukamachi H., Chi X.Z., Wee H.J., Inoue K., Ida H., Bouillet P., Strasser A., Bae S.C., Ito Y. The Runx3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor beta-induced apoptosis. Mol. Cell. Biol. 2006, 26:4474-4488.
24. Lei K., Davis R.J. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:2432-2437.
25. Ley R., Ewings K.E., Hadfield K., Howes E., Balmanno K., Cook S.J. Extracellular signal-regulated kinases 1/2 are serum-stimulated "Bim(EL) kinases" that bind to the Bh3-only protein Bim(EL) causing its phosphorylation and turnover. J. Biol. Chem. 2004, 279:8837-8847.
26. Seward R.J., Von Haller P.D., Aebersold R., Huber B.T. Phosphorylation of the pro-apoptotic protein Bim in lymphocytes is associated with protection from apoptosis. Mol. Immunol. 2003, 39:983-993.
27. Luciano F., Jacquel A., Colosetti P., Herrant M., Cagnol S., Pages G., Auberger P. Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene 2003, 22:6785-6793.
28. Weston C.R., Balmanno K., Chalmers C., Hadfield K., Molton S.A., Ley R., Wagner E.F., Cook S.J. Activation of Erk1/2 by deltaraf-1:Er* represses Bim expression independently of the JNK or Pi3k pathways. Oncogene 2003, 22:1281-1293.
29. Hubner A., Barrett T., Flavell R.A., Davis R.J. Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol. Cell 2008, 30:415-425.
30. Leung K.T., Li K.K., Sun S.S., Chan P.K., Ooi V.E., Chiu L.C. Activation of the JNK pathway promotes phosphorylation and degradation of BimEL-a novel mechanism of chemoresistance in T-cell acute lymphoblastic leukemia. Carcinogenesis 2008, 29:544-551.
31. Li W.Q., Guszczynski T., Hixon J.A., Durum S.K. Interleukin-7 regulates Bim proapoptotic activity in peripheral T-cell survival. Mol. Cell. Biol. 2010, 30:590-600.
32. O'Connor L., Strasser A., O'Reilly L.A., Hausmann G., Adams J.M., Cory S., Huang D.C. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998, 17:384-395.
33. Miyashita U.M.T., Shikama Y., Tadokoro K., Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001, 509:135-141.
34. Adachi M., Zhao X., Imai K. Nomenclature of dynein light chain-linked Bh3-only protein Bim isoforms. Cell Death Differ. 2005, 12:192-193.
35. Hubbard V.M., Valdor R., Patel B., Singh R., Cuervo A.M., Macian F. Macroautophagy regulates energy metabolism during effector T cell activation. J. Immunol. 2010, 185:7349-7357.
36. Li C., Capan E., Zhao Y., Zhao J., Stolz D., Watkins S.C., Jin S., Macian F. Autophagy is induced in Cd4+ T cells and important for the growth factor-withdrawal cell death. J. Immunol. 2006, 177:5163-5168.
37. Kim K., Khaled A.R., Reynolds D., Young H.A., Lee C.K., Durum S.K. Characterization of an interleukin-7-dependent thymic cell line derived from a P53(-/-) mouse. J. Immunol. Methods 2003, 274:177-184.
38. Li W.Q., Jiang Q., Khaled A.R., Keller J.R., Durum S.K. Interleukin-7 inactivates the pro-apoptotic protein Bad promoting T cell survival. J. Biol. Chem. 2004, 279:29160-29166.
39. Jiang Q., Li W.Q., Hofmeister R.R., Young H.A., Hodge D.R., Keller J.R., Khaled A.R., Durum S.K. Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members. Mol. Cell. Biol. 2004, 24:6501-6513.
40. Khaled A.R., Bulavin D.V., Kittipatarin C., Li W.Q., Alvarez M., Kim K., Young H.A., Fornace A.J., Durum S.K. Cytokine-driven cell cycling is mediated through Cdc25a. J. Cell Biol. 2005, 169:755-763.
41. Chehtane M., Khaled A.R. Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the Hexokinase II gene. Am. J. Physiol. Cell Physiol. 2010, 298:C1560-C1571.
42. Kittipatarin C., Khaled A.R. Ex vivo expansion of memory CD8 T cells from lymph nodes or spleen through in vitro culture with interleukin-7. J. Immunol. Methods 2009, 344:45-57.
43. Kittipatarin C., Tschammer N., Khaled A.R. The interaction of LCK and the CD4 co-receptor alters the dose response of T-cells to interleukin-7. Immunol. Lett. 2010, 131:170-181.
44. Kittipatarin C., Li W., Durum S.K., Khaled A.R. Cdc25a-driven proliferation regulates Cd62l levels and lymphocyte movement in response to interleukin-7. Exp. Hematol. 2010, 38:1143-1156.
45. Grenier A.L., Bu-Ihweij K., Zhang G., Moore S., Boohaker R., Slepkov E., Pridemore K., Ren J.J., Fliegel L., Khaled A.R. Apoptosis-induced alkalinization by the Na+/H+ exchanger isoform 1 is mediated through phosphorylation of amino acids Ser726 and Ser729. Am. J. Physiol. Cell Physiol. 2008, 295:C883-C896.
46. Franck P., Petitipain N., Cherlet M., Dardennes M., Maachi F., Schutz B., Poisson L., Nabet P. Measurement of intracellular pH in cultured cells by flow cytometry with BCECF. Am. J Biotechnol. 1996, 46:187-195.
47. Willis S.N., Adams J.M. Life in the balance: how Bh3-only proteins induce apoptosis. Curr. Opin. Cell Biol. 2005, 17:617-625.
48. Seddon B., Zamoyska R. TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells. J. Immunol. 2002, 169:3752-3759.
49. Li W.Q., Jiang Q., Aleem E., Kaldis P., Khaled A.R., Durum S.K. IL-7 promotes T cell proliferation through destabilization of P27kip1. J. Exp. Med. 2006, 203:573-582.
50. Khaled A.R., Durum S.K. Death and baxes: mechanisms of lymphotrophic cytokines. Immunol. Rev. 2003, 193:48-57.
51. Reinhardt H.C., Schumacher B. The P53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet. 2012, 28:128-136.
52. Komarov P.G., Komarova E.A., Kondratov R.V., Christov-Tselkov K., Coon J.S., Chernov M.V., Gudkov A.V. A chemical inhibitor of P53 that protects mice from the side effects of cancer therapy. Science 1999, 285:1733-1737.
53. Sohn D., Graupner V., Neise D., Essmann F., Schulze-Osthoff K., Janicke R.U. Pifithrin-alpha protects against DNA damage-induced apoptosis downstream of mitochondria independent of P53. Cell Death Differ. 2009, 16:869-878.
54. Mazzucchelli R., Durum S.K. Interleukin-7 receptor expression: intelligent design. Nat. Rev. Immunol. 2007, 7:144-154.
55. Turk B., Turk V. Lysosomes as "suicide bags" in cell death: myth or reality?. J. Biol. Chem. 2009, 284:21783-21787.
56. Nilsson C., Johansson U., Johansson A.C., Kagedal K., Ollinger K. Cytosolic acidification and lysosomal alkalinization during TNF-alpha induced apoptosis in U937 cells. Apoptosis 2006, 11:1149-1159.
57. Pedersen S.F. The Na (+)/H (+) exchanger Nhe1 in stress-induced signal transduction: implications for cell proliferation and cell death. Pflugers Arch. 2006, 452:249-259.
58. Gonzalez-Polo R.A., Niso-Santano M., Ortiz-Ortiz M.A., Gomez-Martin A., Moran J.M., Garcia-Rubio L., Francisco-Morcillo J., Zaragoza C., Soler G., Fuentes J.M. Inhibition of paraquat-induced autophagy accelerates the apoptotic cell death in neuroblastoma Sh-Sy5y cells. Toxicol. Sci. 2007, 97:448-458.
59. Shen H.M., Codogno P. Autophagic cell death: Loch Ness monster or endangered species?. Autophagy 2011, 7.
60. Wu Y.T., Tan H.L., Shui G., Bauvy C., Huang Q., Wenk M.R., Ong C.N., Codogno P., Shen H.M. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 2010, 285:10850-10861.
61. Kabeya Y., Mizushima N., Ueno T., Yamamoto A., Kirisako T., Noda T., Kominami E., Ohsumi Y., Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19:5720-5728.
62. Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y., Yoshimori T. LC3, Gabarap and Gate16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 2004, 117:2805-2812.
63. Itakura E., Mizushima N. P62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding. J. Cell Biol. 2011, 192:17-27.
64. Gonzalez-Noriega A., Grubb J.H., Talkad V., Sly W.S. Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J. Cell Biol. 1980, 85:839-852.
65. He Y., Xu Y., Zhang C., Gao X., Dykema K.J., Martin K.R., Ke J., Hudson E.A., Khoo S.K., Resau J.H., Alberts A.S., Mackeigan J.P., Furge K.A., Xu H.E. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci. Signal. 2011, 4:Ra44.
66. Meikle P.J., Brooks D.A., Ravenscroft E.M., Yan M., Williams R.E., Jaunzems A.E., Chataway T.K., Karageorgos L.E., Davey R.C., Boulter C.D., Carlsson S.R., Hopwood J.J. Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated membrane protein LAMP-1 as a diagnostic marker. Clin. Chem. 1997, 43:1325-1335.
67. Putcha G.V., Le S., Frank S., Besirli C.G., Clark K., Chu B., Alix S., Youle R.J., Lamarche A., Maroney A.C., Johnson E.M. JNK-mediated Bim phosphorylation potentiates Bax-dependent apoptosis. Neuron 2003, 38:899-914.
68. Droga-Mazovec G., Bojic L., Petelin A., Ivanova S., Romih R., Repnik U., Salvesen G.S., Stoka V., Turk V., Turk B. Cysteine cathepsins trigger caspase-dependent cell death through cleavage of Bid and antiapoptotic Bcl-2 homologues. J. Biol. Chem. 2008, 283:19140-19150.
69. Berg T.O., Fengsrud M., Stromhaug P.E., Berg T., Seglen P.O. Isolation and characterization of rat liver amphisomes. Evidence for fusion of autophagosomes with both early and late endosomes. J. Biol. Chem. 1998, 273:21883-21892.
70. Qiao L., Zhang J. Inhibition of lysosomal functions reduces proteasomal activity. Neurosci. Lett. 2009, 456:15-19.
71. Isogai S., Morimoto D., Arita K., Unzai S., Tenno T., Hasegawa J., Sou Y.S., Komatsu M., Tanaka K., Shirakawa M., Tochio H. Crystal structure of the ubiquitin-associated (UBA) domain of P62 and its interaction with ubiquitin. J. Biol. Chem. 2011, 286:31864-31874.
72. Day C.L., Puthalakath H., Skea G., Strasser A., Barsukov I., Lian L.Y., Huang D.C., Hinds M.G. Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands. Biochem. J. 2004, 377:597-605.
73. Harada A., Takei Y., Kanai Y., Tanaka Y., Nonaka S., Hirokawa N. Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J. Cell Biol. 1998, 141:51-59.
74. Caviston J.P., Zajac A.L., Tokito M., Holzbaur E.L. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes. Mol. Biol. Cell 2011, 22:478-492.
75. Cai Q., Lu L., Tian J.H., Zhu Y.B., Qiao H., Sheng Z.H. Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons. Neuron 2010, 68:73-86.
76. Dijkers P.F., Medema R.H., Lammers J.W., Koenderman L., Coffer P.J. Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr. Biol. 2000, 10:1201-1204.
77. Datta S.R., Brunet A., Greenberg M.E. Cellular survival: a play in three Akts. Genes Dev. 1999, 13:2905-2927.
78. Whitfield J., Neame S.J., Paquet L., Bernard O., Ham J. Dominant-negative C-Jun promotes neuronal survival by reducing Bim expression and inhibiting mitochondrial cytochrome C release. Neuron 2001, 29:629-643.
79. E. Rajnavolgyi, N. Benbernou, K. Muegge, S.K. Durum, IL-7 withdrawal induces a stress pathway activating P38 map kinase and JNK. 2000. Ref Type: Unpublished Work.
80. Khaled A.R., Li W.Q., Huang J., Fry T.J., Khaled A.S., Mackall C.L., Muegge K., Young H.A., Durum S.K. Bax deficiency partially corrects IL-7 receptor alpha deficiency. Immunity 2002, 17:561-573.
81. Henriques C.M., Rino J., Nibbs R.J., Graham G.J., Barata J.T. IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7ralpha in T cells. Blood 2010, 115:3269-3277.
82. Swainson L., Kinet S., Mongellaz C., Sourisseau M., Henriques T., Taylor N. IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway. Blood 2007, 109:1034-1042.
83. Mcleod I.X., Zhou X., Li Q.J., Wang F., He Y.W. The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7ralpha surface expression. J. Immunol. 2011, 187:5051-5061.
84. Clybouw C., Hadji A., Elmchichi B., Auffredou M.T., Leca G., Vazquez A. BimL upregulation induced by BCR cross-linking in BL41 Burkitt's lymphoma results from a splicing mechanism of the BimEL mRNA. Biochem. Biophys. Res. Commun. 2009, 383:32-36.
85. Maiuri M.C., Le T.G., Criollo A., Rain J.C., Gautier F., Juin P., Tasdemir E., Pierron G., Troulinaki K., Tavernarakis N., Hickman J.A., Geneste O., Kroemer G. Functional and physical interaction between Bcl-X(L) and a Bh3-like domain in beclin-1. EMBO J. 2007, 26:2527-2539.
86. Maiuri M.C., Criollo A., Tasdemir E., Vicencio J.M., Tajeddine N., Hickman J.A., Geneste O., Kroemer G. Bh3-only proteins and Bh3 mimetics induce autophagy by competitively disrupting the interaction between beclin 1 and Bcl-2/Bcl-X(L). Autophagy 2007, 3:374-376.
87. Terradillos O., Montessuit S., Huang D.C., Martinou J.C. Direct addition of BimL to mitochondria does not lead to cytochrome C release. FEBS Lett. 2002, 522:29-34.
88. Faber A.C., Corcoran R.B., Ebi H., Sequist L.V., Waltman B.A., Chung E., Incio J., Digumarthy S.R., Pollack S.F., Song Y., Muzikansky A., Lifshits E., Roberge S., Coffman E.J., Benes C.H., Gomez H.L., Baselga J., Arteaga C.L., Rivera M.N., As-Santagata D., Jain R.K., Engelman J.A. Bim expression in treatment-naive cancers predicts responsiveness to kinase inhibitors. Cancer Discov. 2011, 1:352-365.
89. Labelle J.L., Katz S.G., Bird G.H., Gavathiotis E., Stewart M.L., Lawrence C., Fisher J.K., Godes M., Pitter K., Kung A.L., Walensky L.D. A stapled Bim peptide overcomes apoptotic resistance in hematologic cancers. J. Clin. Invest. 2012, 122:2018-2031.