|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3226-3239
Mcl-1 in Transgenic Mice Promotes Survival in a Spectrum of
Hematopoietic Cell Types and Immortalization in the Myeloid Lineage
Ping Zhou,
Liping Qian,
Christine K. Bieszczad,
Randolph Noelle,
Michael Binder,
Norman B. Levy, and
Ruth W. Craig
From the Departments of Pharmacology and Toxicology, Pathology,
Anatomy, and Immunology, Dartmouth Medical School, Hanover, NH.
Mcl-1 is a member of the Bcl-2 family that is expressed in early
monocyte differentiation and that can promote viability on transfection
into immature myeloid cells. However, the effects of Mcl-1 are
generally short lived compared with those of Bcl-2 and are not obvious
in some transfectants. To further explore the effects of this gene,
mice were produced that expressed Mcl-1 as a transgene in
hematolymphoid tissues. The Mcl-1 transgene was found to cause moderate
viability enhancement in a wide range of hematopoietic cell types,
including lymphoid (B and T) as well as myeloid cells at both immature
and mature stages of differentiation. However, enhanced hematopoietic
capacity in transgenic bone marrow and spleen was not reflected in any
change in pool sizes in the peripheral blood. In addition, among
transgenic cells, mature T cells remained long lived compared with B
cells and macrophages could live longer than either of these.
Interestingly, when hematopoietic cells were maintained in tissue
culture in the presence of interleukin-3, Mcl-1 enhanced the
probability of outgrowth of continuously proliferating myeloid cell
lines. Thus, Mcl-1 transgenic cells remained subject to normal in vivo
homeostatic mechanisms controlling viable cell number, but these
constraints could be overridden under specific conditions in vitro.
Within the organism, Bcl-2 family members may act at "viability
gates" along the differentiation continuum, functioning as part of a
system for controlled hematopoietic cell amplification. Enforced
expression of even a moderate viability-promoting member of this family
such as Mcl-1, within a conducive intra- and extracellular environment
in isolation from normal homeostatic constraints, can substantially
increase the probability of cell immortalization.
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Chopra, J. S. Reuben, and A. C. Sharma
Acute Lung Injury:Apoptosis and Signaling Mechanisms
Experimental Biology and Medicine,
April 1, 2009;
234(4):
361 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Germain and V. Duronio
The N Terminus of the Anti-apoptotic BCL-2 Homologue MCL-1 Regulates Its Localization and Function
J. Biol. Chem.,
November 2, 2007;
282(44):
32233 - 32242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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.
N-terminal Truncation of Antiapoptotic MCL1, but Not G2/M-induced Phosphorylation, Is Associated with Stabilization and Abundant Expression in Tumor Cells
J. Biol. Chem.,
August 17, 2007;
282(33):
23919 - 23936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Soleymanlou, A. Jurisicova, Y. Wu, M. Chijiiwa, J. E. Ray, J. Detmar, T. Todros, S. Zamudio, M. Post, and I. Caniggia
Hypoxic Switch in Mitochondrial Myeloid Cell Leukemia Factor-1/Mtd Apoptotic Rheostat Contributes to Human Trophoblast Cell Death in Preeclampsia
Am. J. Pathol.,
August 1, 2007;
171(2):
496 - 506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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
Serine 64 Phosphorylation Enhances the Antiapoptotic Function of Mcl-1
J. Biol. Chem.,
June 22, 2007;
282(25):
18407 - 18417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal
Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells
Am J Physiol Renal Physiol,
June 1, 2007;
292(6):
F1710 - F1717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Dzhagalov, A. St. John, and Y.-W. He
The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages
Blood,
February 15, 2007;
109(4):
1620 - 1626.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Zhivotovsky and S. Orrenius
Carcinogenesis and apoptosis: paradigms and paradoxes
Carcinogenesis,
October 1, 2006;
27(10):
1939 - 1945.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Basu, V. P. Castle, M. Bouziane, K. Bhalla, and S. Haldar
Crosstalk between Extrinsic and Intrinsic Cell Death Pathways in Pancreatic Cancer: Synergistic Action of Estrogen Metabolite and Ligands of Death Receptor Family.
Cancer Res.,
April 15, 2006;
66(8):
4309 - 4318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liu, P. Eksarko, V. Temkin, G. K. Haines III, H. Perlman, A. E. Koch, B. Thimmapaya, and R. M. Pope
Mcl-1 Is Essential for the Survival of Synovial Fibroblasts in Rheumatoid Arthritis
J. Immunol.,
December 15, 2005;
175(12):
8337 - 8345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rahmani, E. M. Davis, C. Bauer, P. Dent, and S. Grant
Apoptosis Induced by the Kinase Inhibitor BAY 43-9006 in Human Leukemia Cells Involves Down-regulation of Mcl-1 through Inhibition of Translation
J. Biol. Chem.,
October 21, 2005;
280(42):
35217 - 35227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Balakrishnan, W. G. Wierda, M. J. Keating, and V. Gandhi
Mechanisms of Cell Death of Chronic Lymphocytic Leukemia Lymphocytes by RNA-Directed Agent, 8-NH2-Adenosine
Clin. Cancer Res.,
September 15, 2005;
11(18):
6745 - 6752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. W. C. J. van de Donk, D. Schotte, M. M. J. Kamphuis, A. M. W. van Marion, B. van Kessel, A. C. Bloem, and H. M. Lokhorst
Protein Geranylgeranylation Is Critical for the Regulation of Survival and Proliferation of Lymphoma Tumor Cells
Clin. Cancer Res.,
November 15, 2003;
9(15):
5735 - 5748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Karlsson, M. Engstrom, M. Jonsson, P. Karlberg, C. J.H. Pronk, J. Richter, and J.-I. Jonsson
Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes
J. Leukoc. Biol.,
November 1, 2003;
74(5):
923 - 931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Crossley
Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1
J. Leukoc. Biol.,
October 1, 2003;
74(4):
583 - 592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Terskikh, T. Miyamoto, C. Chang, L. Diatchenko, and I. L. Weissman
Gene expression analysis of purified hematopoietic stem cells and committed progenitors
Blood,
July 1, 2003;
102(1):
94 - 101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liu, Y. Ma, S. M. Cole, C. Zander, K.-H. Chen, J. Karras, and R. M. Pope
Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival
Blood,
July 1, 2003;
102(1):
344 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Woltman, S. W. van der Kooij, P. J. Coffer, R. Offringa, M. R. Daha, and C. van Kooten
Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression
Blood,
February 15, 2003;
101(4):
1439 - 1445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bae, J. R. Donigian, and A. J. W. Hsueh
Tankyrase 1 Interacts with Mcl-1 Proteins and Inhibits Their Regulation of Apoptosis
J. Biol. Chem.,
February 7, 2003;
278(7):
5195 - 5204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhang, F. Li, D. Weidner, Z. H. Mnjoyan, and K. Fujise
Physical and Functional Interaction between Myeloid Cell Leukemia 1 Protein (MCL1) and Fortilin. THE POTENTIAL ROLE OF MCL1 AS A FORTILIN CHAPERONE
J. Biol. Chem.,
September 27, 2002;
277(40):
37430 - 37438.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Vrana, C. K. Bieszczad, E. S. Cleaveland, Y. Ma, J. P. Park, T. K. Mohandas, and R. W. Craig
An MCL1-overexpressing Burkitt Lymphoma Subline Exhibits Enhanced Survival on Exposure to Serum Deprivation, Topoisomerase Inhibitors, or Staurosporine but Remains Sensitive to 1-{beta}-D-Arabinofuranosylcytosine
Cancer Res.,
February 1, 2002;
62(3):
892 - 900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Kupfner, J. J. Arcaroli, H.-K. Yum, S. G. Nadler, K.-Y. Yang, and E. Abraham
Role of NF-{kappa}B in Endotoxemia-Induced Alterations of Lung Neutrophil Apoptosis
J. Immunol.,
December 15, 2001;
167(12):
7044 - 7051.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shinoda, Y. Nakamura, K. Matsushita, K. Shimoda, H. Okita, M. Fukuma, T. Yamada, H. Ohde, Y. Oguchi, J.-i. Hata, et al.
Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene
Br. J. Ophthalmol.,
October 1, 2001;
85(10):
1237 - 1243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liu, H. Perlman, L. J. Pagliari, and R. M. Pope
Constitutively Activated Akt-1 Is Vital for the Survival of Human Monocyte-differentiated Macrophages: Role of Mcl-1, Independent of Nuclear Factor (NF)-{kappa}B, Bad, or Caspase Activation
J. Exp. Med.,
July 9, 2001;
194(2):
113 - 126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. K. Epling-Burnette, B. Zhong, F. Bai, K. Jiang, R. D. Bailey, R. Garcia, R. Jove, J. Y. Djeu, T. P. Loughran Jr., and S. Wei
Cooperative Regulation of Mcl-1 by Janus Kinase/STAT and Phosphatidylinositol 3-Kinase Contribute to Granulocyte-Macrophage Colony-Stimulating Factor-Delayed Apoptosis in Human Neutrophils
J. Immunol.,
June 15, 2001;
166(12):
7486 - 7495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zhou, N. B. Levy, H. Xie, L. Qian, C.-Y. G. Lee, R. D. Gascoyne, and R. W. Craig
MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes
Blood,
June 15, 2001;
97(12):
3902 - 3909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Suzuki, S.-i. Hashimoto, N. Toyoda, S. Nagai, N. Yamazaki, H.-Y. Dong, J. Sakai, T. Yamashita, T. Nukiwa, and K. Matsushima
Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE
Blood,
October 1, 2000;
96(7):
2584 - 2591.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Josefsen, J. H. Myklebust, J. Lømo, M. Sioud, H. K. Blomhoff, and E. B. Smeland
Differential Expression of Bcl-2 Homologs in Human CD34+ Hematopoietic Progenitor Cells Induced to Differentiate into Erythroid or Granulocytic Cells
Stem Cells,
July 1, 2000;
18(4):
261 - 272.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. L. Rinkenberger, S. Horning, B. Klocke, K. Roth, and S. J. Korsmeyer
Mcl-1 deficiency results in peri-implantation embryonic lethality
Genes & Dev.,
January 1, 2000;
14(1):
23 - 27.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. P. Leo, S. Y. Hsu, S.-Y. Chun, H.-W. Bae, and A. J. W. Hsueh
Characterization of the Antiapoptotic Bcl-2 Family Member Myeloid Cell Leukemia-1 (Mcl-1) and the Stimulation of Its Message by Gonadotropins in the Rat Ovary
Endocrinology,
December 1, 1999;
140(12):
5469 - 5477.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. J. Townsend, P. Zhou, L. Qian, C. K. Bieszczad, C. H. Lowrey, A. Yen, and R. W. Craig
Regulation of MCL1 through a Serum Response Factor/Elk-1-mediated Mechanism Links Expression of a Viability-promoting Member of the BCL2 Family to the Induction of Hematopoietic Cell Differentiation
J. Biol. Chem.,
January 15, 1999;
274(3):
1801 - 1813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Bingle, R. W. Craig, B. M. Swales, V. Singleton, P. Zhou, and M. K. B. Whyte
Exon Skipping in Mcl-1 Results in a Bcl-2 Homology Domain 3 Only Gene Product That Promotes Cell Death
J. Biol. Chem.,
July 14, 2000;
275(29):
22136 - 22146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bae, C. P. Leo, S. Y. Hsu, and A. J. W. Hsueh
MCL-1S, a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1, Encodes a Proapoptotic Protein Possessing Only the BH3 Domain
J. Biol. Chem.,
August 11, 2000;
275(33):
25255 - 25261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
