Dr. Josef Steiner Cancer Research Prize Lecture: The role of physiological cell death in neoplastic transformation and in anti-cancer therapy

Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics

1972 • 15,349 citations

p53 Mutations in Human Cancers

1991 • 8,133 citations

Caspases: Enemies Within

1998 • 6,923 citations

Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death

1993 • 6,009 citations

Death Receptors: Signaling and Modulation

1998 • 5,873 citations

Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery

1997 • 5,665 citations

The Bcl-2 Protein Family: Arbiters of Cell Survival

1998 • 5,359 citations

Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours

1992 • 4,648 citations

Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis

1998 • 4,383 citations

The p53 tumour suppressor gene

1991 • 3,871 citations

Bid, a Bcl2 Interacting Protein, Mediates Cytochrome c Release from Mitochondria in Response to Activation of Cell Surface Death Receptors

1998 • 3,603 citations

Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells

1988 • 3,194 citations

A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD

1998 • 3,169 citations

bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death

1993 • 3,111 citations

A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia

1992 • 3,092 citations

Induction of apoptosis in fibroblasts by c-myc protein

1992 • 2,977 citations

p53-dependent apoptosis modulates the cytotoxicity of anticancer agents

1993 • 2,969 citations

Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis

1992 • 2,932 citations

p53 is required for radiation-induced apoptosis in mouse thymocytes

1993 • 2,911 citations

Programmed Cell Death in Animal Development

1997 • 2,690 citations

Serine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL

1996 • 2,627 citations

Mechanisms and Genes of Cellular Suicide

1995 • 2,514 citations

The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme

1993 • 2,484 citations

Thymocyte apoptosis induced by p53-dependent and independent pathways

1993 • 2,322 citations

Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt

1997 • 2,245 citations

Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor.

1995 • 2,142 citations

Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death

1995 • 2,114 citations

Mechanisms and Functions of Cell Death

1991 • 2,061 citations

A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B

1997 • 2,054 citations

Tumor spectrum analysis in p53-mutant mice

1994 • 2,034 citations

Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice

1996 • 1,902 citations

DFF, a Heterodimeric Protein That Functions Downstream of Caspase-3 to Trigger DNA Fragmentation during Apoptosis

1997 • 1,848 citations

Involvement of the bcl -2 Gene in Human Follicular Lymphoma

1985 • 1,797 citations

Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice

1994 • 1,772 citations

Cloning of the Chromosome Breakpoint of Neoplastic B Cells with the t(14;18) Chromosome Translocation

1984 • 1,761 citations

Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9

1998 • 1,642 citations

Generalized lymphoproliferative disease in mice, caused by a point mutation in the fas ligand

1994 • 1,549 citations

Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome

1995 • 1,477 citations

Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53

1992 • 1,358 citations

Somatic Frameshift Mutations in the BAX Gene in Colon Cancers of the Microsatellite Mutator Phenotype

1997 • 1,329 citations

Mutations in Fas Associated with Human Lymphoproliferative Syndrome and Autoimmunity

1995 • 1,306 citations

Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo

1998 • 1,292 citations

bcl-2-Immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation

1989 • 1,252 citations

Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation

1986 • 1,232 citations

Targeted Disruption of the Mouse Caspase 8 Gene Ablates Cell Death Induction by the TNF Receptors, Fas/Apo1, and DR3 and Is Lethal Prenatally

1998 • 1,224 citations

bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes

1991 • 1,223 citations

FLICE is activated by association with the CD95 death-inducing signaling complex (DISC)

1997 • 1,207 citations

Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18

1985 • 1,188 citations

Bim: a novel member of the Bcl-2 family that promotes apoptosis

1998 • 1,154 citations

C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2

1994 • 1,145 citations

Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development

1998 • 1,143 citations

Autoactivation of Procaspase-9 by Apaf-1-Mediated Oligomerization

1998 • 1,132 citations

Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles

1992 • 1,117 citations

The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells

1989 • 1,097 citations

bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship

1991 • 1,090 citations

Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways

1994 • 1,073 citations

Expression of baculovirus P35 prevents cell death in Drosophila

1994 • 1,037 citations

An Induced Proximity Model for Caspase-8 Activation

1998 • 1,030 citations

Apoptotic cell death induced by c-myc is inhibited by bcl-2

1992 • 981 citations

Programmed cell death

1974 • 966 citations

The molecular biology of apoptosis.

1996 • 963 citations

MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.

1993 • 959 citations

BID: a novel BH3 domain-only death agonist.

1996 • 921 citations

Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2

1990 • 910 citations

Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development

1998 • 894 citations

FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis

1998 • 893 citations

Caenorhabditis elegans gene ced-9 protects cells from programmed cell death

1992 • 889 citations

Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease.

1991 • 876 citations

Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18)

1991 • 876 citations

Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis.

1991 • 861 citations

Structure and mechanism of interleukin-lβ converting enzyme

1994 • 842 citations

Checkpoints of dueling dimers foil death wishes

1994 • 806 citations

Daxx, a Novel Fas-Binding Protein That Activates JNK and Apoptosis

1997 • 797 citations

Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.

1995 • 791 citations

Cooperative interaction between c-myc and bcl-2 proto-oncogenes

1992 • 766 citations

An evolutionary perspective on apoptosis

1994 • 758 citations

Induction of apoptosis by the Bcl-2 homologue Bak

1995 • 738 citations

High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy

1993 • 738 citations

Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1

1998 • 704 citations

DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2

1994 • 671 citations

Bax suppresses tumorigenesis and stimulates apoptosis in vivo

1997 • 648 citations

Interaction of CED-4 with CED-3 and CED-9: A Molecular Framework for Cell Death

1997 • 635 citations

The C. elegans Protein EGL-1 Is Required for Programmed Cell Death and Interacts with the Bcl-2–like Protein CED-9

1998 • 628 citations

Prevention of Programmed Cell Death in Caenorhabditis elegans by Human bcl-2

1992 • 608 citations

Bcl-2 Rescues T Lymphopoiesis in Interleukin-7 Receptor–Deficient Mice

1997 • 603 citations

Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer

1994 • 567 citations

Cell Growth & Differentiation

1992 • 558 citations

RAIDD is a new 'death' adaptor molecule

1997 • 547 citations

Bcl-X _L interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation

1998 • 534 citations

Caspase-9, Bcl-XL, and Apaf-1 Form a Ternary Complex

1998 • 523 citations

Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak

1995 • 514 citations

A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes

1998 • 504 citations

Bcl-2 Can Rescue T Lymphocyte Development in Interleukin-7 Receptor–Deficient Mice but Not in Mutant rag-1 −/− Mice

1997 • 503 citations

Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K

1995 • 501 citations

bcl-2 gene transfer increases relative resistance of S49.1 and WEHI7.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs.

1992 • 487 citations

The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis

1996 • 434 citations

Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins.

1995 • 431 citations

Bcl-XL and Bcl-2 repress a common pathway of cell death.

1995 • 406 citations

The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry.

1996 • 384 citations

harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-XL

1997 • 381 citations

Membrane Oligomerization and Cleavage Activates the Caspase-8 (FLICE/MACHα1) Death Signal

1998 • 366 citations

Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members

1997 • 357 citations

Ultrastructural localization of bcl-2 protein.

1992 • 351 citations

The bcl-2 candidate proto-oncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation.

1989 • 349 citations

Interaction and Regulation of Subcellular Localization of CED-4 by CED-9

1997 • 345 citations

Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation.

1996 • 344 citations

The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry

1997 • 343 citations

The mouse fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster

1994 • 335 citations

Somatic Fas Mutations in Non-Hodgkin’s Lymphoma: Association With Extranodal Disease and Autoimmunity

1998 • 324 citations

bcl-w, a novel member of the bcl-2 family, promotes cell survival.

1996 • 309 citations

Interaction between the C. elegans cell-death regulators CED-9 and CED-4

1997 • 304 citations

Fusion of the Leucine Zipper Gene HLF to the E2A Gene in Human Acute B-Lineage Leukemia

1992 • 290 citations

Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.

1996 • 284 citations

Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis

1998 • 269 citations

p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following gamma-irradiation.

1994 • 264 citations

Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death

1997 • 248 citations

Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities.

1996 • 236 citations

Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia.

1992 • 234 citations

The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the outer mitochondrial membrane.

1994 • 233 citations

A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia.

1984 • 227 citations

Baculovirus p35 prevents developmentally programmed cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans.

1994 • 204 citations

Size Control: The Regulation of Cell Numbers in Animal Development

1996 • 202 citations

Characterization of the protein product of bcl-2, the gene involved in human follicular lymphoma.

1987 • 191 citations

Spontaneous Development of Plasmacytoid Tumors in Mice with Defective Fas–Fas Ligand Interactions

1998 • 181 citations

The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy

1997 • 179 citations

Bcl-2 blocks glucocorticoid- but not Fas- or activation-induced apoptosis in a T cell hybridoma.

1995 • 178 citations

CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease.

1996 • 174 citations

Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2

1996 • 164 citations

E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells.

1993 • 162 citations

Bcl-2 expression promotes B- but not T-lymphoid development in scid mice

1994 • 157 citations

A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation

1996 • 153 citations

Mcl-1 in Transgenic Mice Promotes Survival in a Spectrum of Hematopoietic Cell Types and Immortalization in the Myeloid Lineage

1998 • 151 citations

Positive and negative selection of T cells in T-cellreceptor transgenic mice expressing a bcl-2 transgene.

1994 • 147 citations

Membrane topology of the Bcl-2 proto-oncogenic protein demonstrated in vitro.

1990 • 147 citations

Mutation of CD95 (Fas/Apo-1) Gene in Adult T-Cell Leukemia Cells

1998 • 130 citations

Reversal of apoptosis by the leukaemia-associated E2A–HLF chimaeric transcription factor

1996 • 129 citations

Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes

1995 • 126 citations

Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene.

1988 • 121 citations

CD95 (APO-1/Fas) Mutations in Childhood T-Lineage Acute Lymphoblastic Leukemia

1998 • 121 citations

Blk, a BH3-containing Mouse Protein That Interacts with Bcl-2 and Bcl-xL, Is a Potent Death Agonist

1998 • 113 citations

Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity.

1993 • 109 citations

Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma.

1988 • 105 citations

Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice

1995 • 92 citations

Life and death during lymphocyte development and function: evidence for two distinct killing mechanisms

1995 • 85 citations

Expression of a bcl-2 transgene reduces proliferation and slows turnover of developing B lymphocytes in vivo.

1997 • 82 citations

Progenitor tumours from Emu-bcl-2-myc transgenic mice have lymphomyeloid differentiation potential and reveal developmental differences in cell survival.

1996 • 67 citations

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

1997 • 49 citations

Collaboration of PIM-1 and BCL-2 in Lymphomagenesis

1992 • 46 citations

Growth of E mu-myc transgenic B-lymphoid cells in vitro and their evolution toward autonomy.

1988 • 34 citations