Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 307 (5712): 1101-1104

Copyright © 2005 by the American Association for the Advancement of Science

Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells

Joseph T. Opferman,1,2* Hiromi Iwasaki,2 Christy C. Ong,1,2 Heikyung Suh,1,2 Shin-ichi Mizuno,2 Koichi Akashi,2{dagger} Stanley J. Korsmeyer1,2{dagger}

Abstract: Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia–1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.

1 Howard Hughes Medical Institute, Department of Cancer Immunology and AIDS, Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.
2 Dana Farber Cancer Institute, Department of Cancer Immunology and AIDS, Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.

* Present address: Department of Biochemistry, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.

{dagger} To whom correspondence should be addressed. E-mail: Koichi_Akashi{at} (K.A.); Stanley_Korsmeyer{at} (S.K.)

Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia.
R. Pan, L. J. Hogdal, J. M. Benito, D. Bucci, L. Han, G. Borthakur, J. Cortes, D. J. DeAngelo, L. Debose, H. Mu, et al. (2014)
Cancer Discovery 4, 362-375
   Abstract »    Full Text »    PDF »
Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons.
E. M. Pietras, R. Lakshminarasimhan, J.-M. Techner, S. Fong, J. Flach, M. Binnewies, and E. Passegue (2014)
J. Exp. Med. 211, 245-262
   Abstract »    Full Text »    PDF »
Enhanced stability of Mcl1, a prosurvival Bcl2 relative, blunts stress-induced apoptosis, causes male sterility, and promotes tumorigenesis.
T. Okamoto, L. Coultas, D. Metcalf, M. F. van Delft, S. P. Glaser, M. Takiguchi, A. Strasser, P. Bouillet, J. M. Adams, and D. C. S. Huang (2014)
PNAS 111, 261-266
   Abstract »    Full Text »    PDF »
Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53.
G. L. Kelly, S. Grabow, S. P. Glaser, L. Fitzsimmons, B. J. Aubrey, T. Okamoto, L. J. Valente, M. Robati, L. Tai, W. D. Fairlie, et al. (2014)
Genes & Dev. 28, 58-70
   Abstract »    Full Text »    PDF »
Notchless-dependent ribosome synthesis is required for the maintenance of adult hematopoietic stem cells.
M. Le Bouteiller, C. Souilhol, S. Beck-Cormier, A. Stedman, O. Burlen-Defranoux, S. Vandormael-Pournin, F. Bernex, A. Cumano, and M. Cohen-Tannoudji (2013)
J. Exp. Med. 210, 2351-2369
   Abstract »    Full Text »    PDF »
Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia.
B. Koss, J. Morrison, R. M. Perciavalle, H. Singh, J. E. Rehg, R. T. Williams, and J. T. Opferman (2013)
Blood 122, 1587-1598
   Abstract »    Full Text »    PDF »
Targeting apoptosis to induce stable mixed hematopoietic chimerism and long-term allograft survival without myelosuppressive conditioning in mice.
P. E. Cippa, S. S. Gabriel, J. Chen, P. D. Bardwell, A. Bushell, A. Guimezanes, A. K. Kraus, T. Wekerle, R. P. Wuthrich, and T. Fehr (2013)
Blood 122, 1669-1677
   Abstract »    Full Text »    PDF »
Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1.
S. M. M. Hasan, A. D. Sheen, A. M. Power, L. M. Langevin, J. Xiong, M. Furlong, K. Day, C. Schuurmans, J. T. Opferman, and J. L. Vanderluit (2013)
Development 140, 3118-3127
   Abstract »    Full Text »    PDF »
Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction.
X. Wang, M. Bathina, J. Lynch, B. Koss, C. Calabrese, S. Frase, J. D. Schuetz, J. E. Rehg, and J. T. Opferman (2013)
Genes & Dev. 27, 1351-1364
   Abstract »    Full Text »    PDF »
Apc regulates the function of hematopoietic stem cells largely through {beta}-catenin-dependent mechanisms.
W. Li, Y. Hou, M. Ming, L. Yu, A. Seba, and Z. Qian (2013)
Blood 121, 4063-4072
   Abstract »    Full Text »    PDF »
RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an E{mu}-myc/Bcl-2 mouse model.
J. R. Mills, A. Malina, T. Lee, D. Di Paola, O. Larsson, C. Miething, F. Grosse, H. Tang, M. Zannis-Hadjopoulos, S. W. Lowe, et al. (2013)
Blood 121, 3402-3412
   Abstract »    Full Text »    PDF »
Programming cancer cells for high expression levels of Mcl1.
F. Ertel, M. Nguyen, A. Roulston, and G. C. Shore (2013)
EMBO Rep. 14, 328-336
   Abstract »    Full Text »    PDF »
Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf.
V. Labi, D. Bertele, C. Woess, D. Tischner, F. J. Bock, S. Schwemmers, H. L. Pahl, S. Geley, M. Kunze, C. M. Niemeyer, et al. (2013)
EMBO Mol Med. 5, 122-136
   Abstract »    Full Text »    PDF »
Mithramycin A Inhibits Myeloid Cell Leukemia-1 to Induce Apoptosis in Oral Squamous Cell Carcinomas and Tumor Xenograft through Activation of Bax and Oligomerization.
J.-A. Shin, J.-Y. Jung, M. H. Ryu, S. Safe, and S.-D. Cho (2013)
Mol. Pharmacol. 83, 33-41
   Abstract »    Full Text »    PDF »
The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function.
V. Krasteva, M. Buscarlet, A. Diaz-Tellez, M.-A. Bernard, G. R. Crabtree, and J. A. Lessard (2012)
Blood 120, 4720-4732
   Abstract »    Full Text »    PDF »
Human Cytomegalovirus Stimulates Monocyte-to-Macrophage Differentiation via the Temporal Regulation of Caspase 3.
G. Chan, M. T. Nogalski, and A. D. Yurochko (2012)
J. Virol. 86, 10714-10723
   Abstract »    Full Text »    PDF »
Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells.
T. Asai, Y. Liu, S. Di Giandomenico, N. Bae, D. Ndiaye-Lobry, A. Deblasio, S. Menendez, Y. Antipin, B. Reva, R. Wevrick, et al. (2012)
Blood 120, 1601-1612
   Abstract »    Full Text »    PDF »
The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO.
F.-S. Chou, A. Griesinger, M. Wunderlich, S. Lin, K. A. Link, M. Shrestha, S. Goyama, B. Mizukawa, S. Shen, G. Marcucci, et al. (2012)
Blood 120, 709-719
   Abstract »    Full Text »    PDF »
Mcl-1 and Bcl-xL coordinately regulate megakaryocyte survival.
M. A. Debrincat, E. C. Josefsson, C. James, K. J. Henley, S. Ellis, M. Lebois, K. L. Betterman, R. M. Lane, K. L. Rogers, M. J. White, et al. (2012)
Blood 119, 5850-5858
   Abstract »    Full Text »    PDF »
Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumors.
G. J. Gores and S. H. Kaufmann (2012)
Genes & Dev. 26, 305-311
   Abstract »    Full Text »    PDF »
Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia.
S. P. Glaser, E. F. Lee, E. Trounson, P. Bouillet, A. Wei, W. D. Fairlie, D. J. Izon, J. Zuber, A. R. Rappaport, M. J. Herold, et al. (2012)
Genes & Dev. 26, 120-125
   Abstract »    Full Text »    PDF »
Human cytomegalovirus activation of ERK and myeloid cell leukemia-1 protein correlates with survival of latently infected cells.
M. B. Reeves, A. Breidenstein, and T. Compton (2012)
PNAS 109, 588-593
   Abstract »    Full Text »    PDF »
Deleting Mcl-1 in mast cells: getting 2 birds with 1 stone.
B. Min (2011)
Blood 118, 6729-6730
   Full Text »    PDF »
TNF-{alpha}/Fas-RIP-1-induced cell death signaling separates murine hematopoietic stem cells/progenitors into 2 distinct populations.
Y. Xiao, H. Li, J. Zhang, A. Volk, S. Zhang, W. Wei, S. Zhang, P. Breslin, and J. Zhang (2011)
Blood 118, 6057-6067
   Abstract »    Full Text »    PDF »
ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.
B. W. Day, B. W. Stringer, M. D. Spanevello, S. Charmsaz, P. R. Jamieson, K. S. Ensbey, J. C. Carter, J. M. Cox, V. J. Ellis, C. L. Brown, et al. (2011)
Neuro Oncology 13, 1202-1212
   Abstract »    Full Text »    PDF »
MCL1 increases primitive thymocyte viability in female mice and promotes thymic expansion into adulthood.
J. Gui, A. J. Morales, S. E. Maxey, K. A. Bessette, N. R. Ratcliffe, J. A. Kelly, and R. W. Craig (2011)
Int. Immunol. 23, 647-659
   Abstract »    Full Text »    PDF »
Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion.
J. M. Perry, X. C. He, R. Sugimura, J. C. Grindley, J. S. Haug, S. Ding, and L. Li (2011)
Genes & Dev. 25, 1928-1942
   Abstract »    Full Text »    PDF »
Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases.
A. Strasser, S. Cory, and J. M. Adams (2011)
EMBO J. 30, 3667-3683
   Abstract »    Full Text »    PDF »
A critical role for SHP2 in STAT5 activation and growth factor-mediated proliferation, survival, and differentiation of human CD34+ cells.
L. Li, H. Modi, T. McDonald, J. Rossi, J.-K. Yee, and R. Bhatia (2011)
Blood 118, 1504-1515
   Abstract »    Full Text »    PDF »
Akt-Dependent Glucose Metabolism Promotes Mcl-1 Synthesis to Maintain Cell Survival and Resistance to Bcl-2 Inhibition.
J. L. Coloff, A. N. Macintyre, A. G. Nichols, T. Liu, C. A. Gallo, D. R. Plas, and J. C. Rathmell (2011)
Cancer Res. 71, 5204-5213
   Abstract »    Full Text »    PDF »
Mitochondrion-dependent N-terminal Processing of Outer Membrane Mcl-1 Protein Removes an Essential Mule/Lasu1 Protein-binding Site.
M. R. Warr, J. R. Mills, M. Nguyen, S. Lemaire-Ewing, J. Baardsnes, K. L. W. Sun, A. Malina, J. C. Young, D. V. Jeyaraju, M. O'Connor-McCourt, et al. (2011)
J. Biol. Chem. 286, 25098-25107
   Abstract »    Full Text »    PDF »
Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells.
Y. Chen, M. Yu, X. Dai, M. Zogg, R. Wen, H. Weiler, and D. Wang (2011)
J. Exp. Med. 208, 923-935
   Abstract »    Full Text »    PDF »
Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells.
G. Chan, L. S. Cheung, W. Yang, M. Milyavsky, A. D. Sanders, S. Gu, W. X. Hong, A. X. Liu, X. Wang, M. Barbara, et al. (2011)
Blood 117, 4253-4261
   Abstract »    Full Text »    PDF »
Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism.
E. Nitta, M. Yamashita, K. Hosokawa, M. Xian, K. Takubo, F. Arai, S. Nakada, and T. Suda (2011)
Blood 117, 4169-4180
   Abstract »    Full Text »    PDF »
Bcr-Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis.
H. Sun, V. Kapuria, L. F. Peterson, D. Fang, W. G. Bornmann, G. Bartholomeusz, M. Talpaz, and N. J. Donato (2011)
Blood 117, 3151-3162
   Abstract »    Full Text »    PDF »
Leukemia Stem Cells and Microenvironment: Biology and Therapeutic Targeting.
M. Y. Konopleva and C. T. Jordan (2011)
J. Clin. Oncol. 29, 591-599
   Abstract »    Full Text »    PDF »
MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner.
M. Germain, A. P. Nguyen, J. N. Le Grand, N. Arbour, J. L. Vanderluit, D. S. Park, J. T. Opferman, and R. S. Slack (2011)
EMBO J. 30, 395-407
   Abstract »    Full Text »    PDF »
FADD Deficiency Impairs Early Hematopoiesis in the Bone Marrow.
S. Rosenberg, H. Zhang, and J. Zhang (2011)
J. Immunol. 186, 203-213
   Abstract »    Full Text »    PDF »
MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.
A. G. L. Ooi, D. Sahoo, M. Adorno, Y. Wang, I. L. Weissman, and C. Y. Park (2010)
PNAS 107, 21505-21510
   Abstract »    Full Text »    PDF »
Quercetin Induces Tumor-Selective Apoptosis through Downregulation of Mcl-1 and Activation of Bax.
S. Cheng, N. Gao, Z. Zhang, G. Chen, A. Budhraja, Z. Ke, Y.-o. Son, X. Wang, J. Luo, and X. Shi (2010)
Clin. Cancer Res. 16, 5679-5691
   Abstract »    Full Text »    PDF »
Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance.
K. J. Campbell, M. L. Bath, M. L. Turner, C. J. Vandenberg, P. Bouillet, D. Metcalf, C. L. Scott, and S. Cory (2010)
Blood 116, 3197-3207
   Abstract »    Full Text »    PDF »
Expression of the Transcriptional Repressor Gfi-1 Is Regulated by C/EBP{alpha} and Is Involved in Its Proliferation and Colony Formation-Inhibitory Effects in p210BCR/ABL-Expressing Cells.
M. R. Lidonnici, A. Audia, A. R. Soliera, M. Prisco, G. Ferrari-Amorotti, T. Waldron, N. Donato, Y. Zhang, R. V. Martinez, T. L. Holyoake, et al. (2010)
Cancer Res. 70, 7949-7959
   Abstract »    Full Text »    PDF »
Adult hematopoietic stem cells require NKAP for maintenance and survival.
A. G. Pajerowski, M. J. Shapiro, K. Gwin, R. Sundsbak, M. Nelson-Holte, K. Medina, and V. S. Shapiro (2010)
Blood 116, 2684-2693
   Abstract »    Full Text »    PDF »
The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity.
C. J. V. Campbell, J. B. Lee, M. Levadoux-Martin, T. Wynder, A. Xenocostas, B. Leber, and M. Bhatia (2010)
Blood 116, 1433-1442
   Abstract »    Full Text »    PDF »
MicroRNA miR-125a controls hematopoietic stem cell number.
S. Guo, J. Lu, R. Schlanger, H. Zhang, J. Y. Wang, M. C. Fox, L. E. Purton, H. H. Fleming, B. Cobb, M. Merkenschlager, et al. (2010)
PNAS 107, 14229-14234
   Abstract »    Full Text »    PDF »
Hemgn is a direct transcriptional target of HOXB4 and induces expansion of murine myeloid progenitor cells.
J. Jiang, H. Yu, Y. Shou, G. Neale, S. Zhou, T. Lu, and B. P. Sorrentino (2010)
Blood 116, 711-719
   Abstract »    Full Text »    PDF »
Mcl-1 Stability Determines Mitotic Cell Fate of Human Multiple Myeloma Tumor Cells Treated with the Kinesin Spindle Protein Inhibitor ARRY-520.
B. J. Tunquist, R. D. Woessner, and D. H. Walker (2010)
Mol. Cancer Ther. 9, 2046-2056
   Abstract »    Full Text »    PDF »
Ubiquitin-Independent Degradation of Antiapoptotic MCL-1.
D. P. Stewart, B. Koss, M. Bathina, R. M. Perciavalle, K. Bisanz, and J. T. Opferman (2010)
Mol. Cell. Biol. 30, 3099-3110
   Abstract »    Full Text »    PDF »
Critical Requirement of GABP{alpha} for Normal T Cell Development.
S. Yu, D.-M. Zhao, R. Jothi, and H.-H. Xue (2010)
J. Biol. Chem. 285, 10179-10188
   Abstract »    Full Text »    PDF »
PI3K-Dependent Upregulation of Mcl-1 by Human Cytomegalovirus Is Mediated by Epidermal Growth Factor Receptor and Inhibits Apoptosis in Short-Lived Monocytes.
G. Chan, M. T. Nogalski, G. L. Bentz, M. S. Smith, A. Parmater, and A. D. Yurochko (2010)
J. Immunol. 184, 3213-3222
   Abstract »    Full Text »    PDF »
FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation.
G. Yoshimoto, T. Miyamoto, S. Jabbarzadeh-Tabrizi, T. Iino, J. L. Rocnik, Y. Kikushige, Y. Mori, T. Shima, H. Iwasaki, K. Takenaka, et al. (2009)
Blood 114, 5034-5043
   Abstract »    Full Text »    PDF »
Activation of Tumor Suppressor Protein p53 Is Required for Theiler's Murine Encephalomyelitis Virus-Induced Apoptosis in M1-D Macrophages.
K.-N. Son, S. Pugazhenthi, and H. L. Lipton (2009)
J. Virol. 83, 10770-10777
   Abstract »    Full Text »    PDF »
Mcl-1 Integrates the Opposing Actions of Signaling Pathways That Mediate Survival and Apoptosis.
C. Morel, S. M. Carlson, F. M. White, and R. J. Davis (2009)
Mol. Cell. Biol. 29, 3845-3852
   Abstract »    Full Text »    PDF »
Context-dependent Bcl-2/Bak Interactions Regulate Lymphoid Cell Apoptosis.
H. Dai, X. W. Meng, S.-H. Lee, P. A. Schneider, and S. H. Kaufmann (2009)
J. Biol. Chem. 284, 18311-18322
   Abstract »    Full Text »    PDF »
Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function.
D. A. Steimer, K. Boyd, O. Takeuchi, J. K. Fisher, G. P. Zambetti, and J. T. Opferman (2009)
Blood 113, 2805-2815
   Abstract »    Full Text »    PDF »
Promoter Knock-In Mutations Reveal a Role of Mcl-1 in Thymocyte-Positive Selection and Tissue or Cell Lineage-Specific Regulation of Mcl-1 Expression.
C.-Y. Yang, N.-H. Lin, J.-M. Lee, C.-Y. Huang, H.-J. Min, J. J.-Y. Yen, N.-S. Liao, and H.-F. Yang-Yen (2009)
J. Immunol. 182, 2959-2968
   Abstract »    Full Text »    PDF »
Mll5 contributes to hematopoietic stem cell fitness and homeostasis.
Y. Zhang, J. Wong, M. Klinger, M. T. Tran, K. M. Shannon, and N. Killeen (2009)
Blood 113, 1455-1463
   Abstract »    Full Text »    PDF »
Glucose Metabolism Attenuates p53 and Puma-dependent Cell Death upon Growth Factor Deprivation.
Y. Zhao, J. L. Coloff, E. C. Ferguson, S. R. Jacobs, K. Cui, and J. C. Rathmell (2008)
J. Biol. Chem. 283, 36344-36353
   Abstract »    Full Text »    PDF »
Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1.
M. A. Kerenyi, F. Grebien, H. Gehart, M. Schifrer, M. Artaker, B. Kovacic, H. Beug, R. Moriggl, and E. W. Mullner (2008)
Blood 112, 3878-3888
   Abstract »    Full Text »    PDF »
A critical role for Apc in hematopoietic stem and progenitor cell survival.
Z. Qian, L. Chen, A. A. Fernald, B. O. Williams, and M. M. Le Beau (2008)
J. Exp. Med. 205, 2163-2175
   Abstract »    Full Text »    PDF »
hKSR-2, a vitamin D-regulated gene, inhibits apoptosis in arabinocytosine-treated HL60 leukemia cells.
X. Wang, R. Patel, and G. P. Studzinski (2008)
Mol. Cancer Ther. 7, 2798-2806
   Abstract »    Full Text »    PDF »
Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells.
D. G. Kent, B. J. Dykstra, J. Cheyne, E. Ma, and C. J. Eaves (2008)
Blood 112, 560-567
   Abstract »    Full Text »    PDF »
TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice.
M. Tang, X. Wei, Y. Guo, P. Breslin, S. Zhang, S. Zhang, W. Wei, Z. Xia, M. Diaz, S. Akira, et al. (2008)
J. Exp. Med. 205, 1611-1619
   Abstract »    Full Text »    PDF »
The Anti-Apoptotic Bcl-2 Family Member Mcl-1 Promotes T Lymphocyte Survival at Multiple Stages.
I. Dzhagalov, A. Dunkle, and Y.-W. He (2008)
J. Immunol. 181, 521-528
   Abstract »    Full Text »    PDF »
Mcl-1 Is a Key Regulator of Apoptosis during CNS Development and after DNA Damage.
N. Arbour, J. L. Vanderluit, J. N. Le Grand, A. Jahani-Asl, V. A. Ruzhynsky, E. C. C. Cheung, M. A. Kelly, A. E. MacKenzie, D. S. Park, J. T. Opferman, et al. (2008)
J. Neurosci. 28, 6068-6078
   Abstract »    Full Text »    PDF »
Human Flt3 Is Expressed at the Hematopoietic Stem Cell and the Granulocyte/Macrophage Progenitor Stages to Maintain Cell Survival.
Y. Kikushige, G. Yoshimoto, T. Miyamoto, T. Iino, Y. Mori, H. Iwasaki, H. Niiro, K. Takenaka, K. Nagafuji, M. Harada, et al. (2008)
J. Immunol. 180, 7358-7367
   Abstract »    Full Text »    PDF »
Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene.
M. Yamashita, M. Kuwahara, A. Suzuki, K. Hirahara, R. Shinnaksu, H. Hosokawa, A. Hasegawa, S. Motohashi, A. Iwama, and T. Nakayama (2008)
J. Exp. Med. 205, 1109-1120
   Abstract »    Full Text »    PDF »
Bcl-2-family proteins and hematologic malignancies: history and future prospects.
J. C. Reed (2008)
Blood 111, 3322-3330
   Abstract »    Full Text »    PDF »
Novel Pro-survival Functions of the Kruppel-like Transcription Factor Egr2 in Promotion of Macrophage Colony-stimulating Factor-mediated Osteoclast Survival Downstream of the MEK/ERK Pathway.
E. W. Bradley, M. M. Ruan, and M. J. Oursler (2008)
J. Biol. Chem. 283, 8055-8064
   Abstract »    Full Text »    PDF »
A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation.
E. F. Lee, P. E. Czabotar, M. F. van Delft, E. M. Michalak, M. J. Boyle, S. N. Willis, H. Puthalakath, P. Bouillet, P. M. Colman, D. C.S. Huang, et al. (2008)
J. Cell Biol. 180, 341-355
   Abstract »    Full Text »    PDF »
Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis.
N. Chetoui, K. Sylla, J.-V. Gagnon-Houde, C. Alcaide-Loridan, D. Charron, R. Al-Daccak, and F. Aoudjit (2008)
Mol. Cancer Res. 6, 42-52
   Abstract »    Full Text »    PDF »
The N Terminus of the Anti-apoptotic BCL-2 Homologue MCL-1 Regulates Its Localization and Function.
M. Germain and V. Duronio (2007)
J. Biol. Chem. 282, 32233-32242
   Abstract »    Full Text »    PDF »
Cited2 is required for normal hematopoiesis in the murine fetal liver.
Y. Chen, P. Haviernik, K. D. Bunting, and Y.-C. Yang (2007)
Blood 110, 2889-2898
   Abstract »    Full Text »    PDF »
The Multikinase Inhibitor Sorafenib Induces Apoptosis in Highly Imatinib Mesylate-Resistant Bcr/Abl+ Human Leukemia Cells in Association with Signal Transducer and Activator of Transcription 5 Inhibition and Myeloid Cell Leukemia-1 Down-Regulation.
M. Rahmani, T. K. Nguyen, P. Dent, and S. Grant (2007)
Mol. Pharmacol. 72, 788-795
   Abstract »    Full Text »    PDF »
N-terminal Truncation of Antiapoptotic MCL1, but Not G2/M-induced Phosphorylation, Is Associated with Stabilization and Abundant Expression in Tumor Cells.
A. De Biasio, J. A. Vrana, P. Zhou, L. Qian, C. K. Bieszczad, K. E. Braley, A. M. Domina, S. J. Weintraub, J. M. Neveu, W. S. Lane, et al. (2007)
J. Biol. Chem. 282, 23919-23936
   Abstract »    Full Text »    PDF »
Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells.
C. G. Leung, Y. Xu, B. Mularski, H. Liu, S. Gurbuxani, and J. D. Crispino (2007)
J. Exp. Med. 204, 1603-1611
   Abstract »    Full Text »    PDF »
Serine 64 Phosphorylation Enhances the Antiapoptotic Function of Mcl-1.
S. Kobayashi, S.-H. Lee, X. W. Meng, J. L. Mott, S. F. Bronk, N. W. Werneburg, R. W. Craig, S. H. Kaufmann, and G. J. Gores (2007)
J. Biol. Chem. 282, 18407-18417
   Abstract »    Full Text »    PDF »
Glycogen Synthase Kinase 3{alpha} and 3{beta} Mediate a Glucose-Sensitive Antiapoptotic Signaling Pathway To Stabilize Mcl-1.
Y. Zhao, B. J. Altman, J. L. Coloff, C. E. Herman, S. R. Jacobs, H. L. Wieman, J. A. Wofford, L. N. Dimascio, O. Ilkayeva, A. Kelekar, et al. (2007)
Mol. Cell. Biol. 27, 4328-4339
   Abstract »    Full Text »    PDF »
Functional Linkage between NOXA and Bim in Mitochondrial Apoptotic Events.
J. Han, L. A. Goldstein, W. Hou, and H. Rabinowich (2007)
J. Biol. Chem. 282, 16223-16231
   Abstract »    Full Text »    PDF »
De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells.
Y. Tadokoro, H. Ema, M. Okano, E. Li, and H. Nakauchi (2007)
J. Exp. Med. 204, 715-722
   Abstract »    Full Text »    PDF »
Structural insights into the degradation of Mcl-1 induced by BH3 domains.
P. E. Czabotar, E. F. Lee, M. F. van Delft, C. L. Day, B. J. Smith, D. C. S. Huang, W. D. Fairlie, M. G. Hinds, and P. M. Colman (2007)
PNAS 104, 6217-6222
   Abstract »    Full Text »    PDF »
Targeting the mast cell: beyond KIT.
C. Akin (2007)
Blood 109, 2674-2675
   Full Text »    PDF »
Mcl-1 Depletion in Apoptosis Elicited by Ionizing Radiation in Peritoneal Resident Macrophages of C3H Mice.
Y. Kubota, K. Kinoshita, K. Suetomi, A. Fujimori, and S. Takahashi (2007)
J. Immunol. 178, 2923-2931
   Abstract »    Full Text »    PDF »
The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages.
I. Dzhagalov, A. St. John, and Y.-W. He (2007)
Blood 109, 1620-1626
   Abstract »    Full Text »    PDF »
Commonly dysregulated genes in murine APL cells.
W. Yuan, J. E. Payton, M. S. Holt, D. C. Link, M. A. Watson, J. F. DiPersio, and T. J. Ley (2007)
Blood 109, 961-970
   Abstract »    Full Text »    PDF »
Anti-Apoptotic MCL-1 Plays a Critical Role in Maintenance of Normal and Malignant Human Hematopoietic Stem Cells through FLT3 Signaling..
G. Yoshimoto, T. Miyamoto, T. Iino, Y. Kikushige, H. Niiro, H. Iwasaki, M. Harada, and K. Akashi (2006)
Blood (ASH Annual Meeting Abstracts) 108, 11
   Abstract »    PDF »
The Protein Kinase C{delta} Catalytic Fragment Targets Mcl-1 for Degradation to Trigger Apoptosis.
L. A. Sitailo, S. S. Tibudan, and M. F. Denning (2006)
J. Biol. Chem. 281, 29703-29710
   Abstract »    Full Text »    PDF »
An Internal EELD Domain Facilitates Mitochondrial Targeting of Mcl-1 via a Tom70-dependent Pathway.
C.-H. Chou, R.-S. Lee, and H.-F. Yang-Yen (2006)
Mol. Biol. Cell 17, 3952-3963
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882