Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Galluzzi, Lorenzo; Vitale, Ilio; Jm, Abrams; Es, Alnemri; Eh, Baehrecke; Mv, Blagosklonny; Dawson, T. Renee; Dawson, VL; Ws, El-Deiry; Fulda, Simone; Gottlieb, Eyal; Green, Douglas R.; Hengartner, Michael O.; Kepp, Oliver; Knight, R A; Kumar, Sharad; Lipton, Stuart A.; Lü, Xiaomei; Madeo, Frank; Malorni, Walter; Mehlen, Patrick; Núñez, Gabriel; Marynen, Peter; Piacentini, Mauro; Dc, Rubinsztein; Shi, Yufang; Simon, Hans‐Uwe; Vandenabeele, Peter; White, Eileen; Yuan, Junying; Zhivotovsky, Boris; Melino, Gerry

doi:10.1038/cdd.2011.96

Cited by 2,204 publications

(2,322 citation statements)

References 182 publications

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“…In any case, the aberrant expression and localization of phosphorylated histone H3, together with other cell cycle deregulation, was followed by cell death. This type of cell death that is triggered by aberrant mitosis and executed either during mitosis or in the subsequent interphase has been referred as mitotic catastrophe [63, 64]. Roninson et al .…”

Section: The Podocyte’s Catastrophe: Lost Cell Cycle Controlmentioning

confidence: 99%

“…So far, at least three different programs of mitotic catastrophe have been described. First, cells can die without exiting mitosis (mitotic death); second, mitotic catastrophe can trigger a lethal pathway that is not executed until cells reaching interphase of the next cell cycle, or third, the cell can exit mitosis and undergo senescence [64]. Of note, in the adult neurons, death by cell cycle is a very slow process that can take from months to years, and might require an additional stimulus to make the transition from cycle to death.…”

Section: The Podocyte’s Catastrophe: Lost Cell Cycle Controlmentioning

confidence: 99%

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Podocyte Mitosis – A Catastrophe

Lasagni

Lazzeri²,

Shankland

et al. 2012

CMM

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Podocyte loss plays a key role in the progression of glomerular disorders towards glomerulosclerosis and chronic kidney disease. Podocytes form unique cytoplasmic extensions, foot processes, which attach to the outer surface of the glomerular basement membrane and interdigitate with neighboring podocytes to form the slit diaphragm. Maintaining these sophisticated structural elements requires an intricate actin cytoskeleton. Genetic, mechanic, and immunologic or toxic forms of podocyte injury can cause podocyte loss, which causes glomerular filtration barrier dysfunction, leading to proteinuria. Cell migration and cell division are two processes that require a rearrangement of the actin cytoskeleton; this rearrangement would disrupt the podocyte foot processes, therefore, podocytes have a limited capacity to divide or migrate. Indeed, all cells need to rearrange their actin cytoskeleton to assemble a correct mitotic spindle and to complete mitosis. Podocytes, even when being forced to bypass cell cycle checkpoints to initiate DNA synthesis and chromosome segregation, cannot complete cytokinesis efficiently and thus usually generate aneuploid podocytes. Such aneuploid podocytes rapidly detach and die, a process referred to as mitotic catastrophe. Thus, detached or dead podocytes cannot be adequately replaced by the proliferation of adjacent podocytes. However, even glomerular disorders with severe podocyte injury can undergo regression and remission, suggesting alternative mechanisms to compensate for podocyte loss, such as podocyte hypertrophy or podocyte regeneration from resident renal progenitor cells. Together, mitosis of the terminally differentiated podocyte rather accelerates podocyte loss and therefore glomerulosclerosis. Finding ways to enhance podocyte regeneration from other sources remains a challenge goal to improve the treatment of chronic kidney disease in the future.

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Section: The Podocyte’s Catastrophe: Lost Cell Cycle Controlmentioning

confidence: 99%

Section: The Podocyte’s Catastrophe: Lost Cell Cycle Controlmentioning

confidence: 99%

Podocyte Mitosis – A Catastrophe

Lasagni

Lazzeri²,

Shankland

et al. 2012

CMM

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“…1 PCD has been described to take place downstream of death receptors of the tumor necrosis factor receptor (TNFR) family, such as TNFR 1 (TNFR1) or Fas (APO-1 or CD95). 2 Beyond cell death, TNFR1 also triggers the activation of nuclear factor-kappa B (NF-κB) and the transcription of a plethora of pro-inflammatory cytokines and pro-survival factors. TNFR1-mediated NF-κB activation relies on a signaling platform called complex I.…”

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confidence: 99%

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

et al. 2015

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NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTβR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex.In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTβR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.

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“…[3][4][5] Apoptosis represents one of the key forms of programmed cell death. 6 Necroptosis is a caspase-independent mode of programmed cell death that typically occurs when essential factors of apoptosis such as caspases are inhibited and is regulated by RIP1 and RIP3. 7 Inhibitor of apoptosis (IAP) proteins are major regulators of cell death and survival processes.…”

mentioning

confidence: 99%

Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia

Opel

Schnaiter

Dodier

et al. 2015

Intl Journal of Cancer

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Inhibitor of apoptosis (IAP) proteins are highly expressed in chronic lymphocytic leukemia (CLL) cells and contribute to evasion of cell death and poor therapeutic response. Here, we report that Smac mimetic BV6 dose-dependently induces cell death in 28 of 51 (54%) investigated CLL samples, while B-cells from healthy donors are largely unaffected. Importantly, BV6 is significantly more effective in prognostic unfavorable cases with, e.g., non-mutated VH status and TP53 mutation than samples with unknown or favorable prognosis. The majority of cases with 17p deletion (10/12) and Fludarabine refractory cases respond to BV6, indicating that BV6 acts independently of p53. BV6 also triggers cell death under survival conditions mimicking the microenvironment, e.g., by adding CD40 ligand or conditioned medium. Gene expression profiling identifies cell death, NF-jB and redox signaling among the top pathways regulated by BV6 not only in CLL but also in core-binding factor (CBF) acute myeloid leukemia (AML). Consistently, BV6 stimulates production of reactive oxygen species (ROS), which are contributing to BV6-induced cell death, since antioxidants reduce cell death. While BV6 causes degradation of cellular inhibitor of apoptosis (cIAP)1 and cIAP2 and nuclear factor-kappaB (NF-jB) pathway activation in primary CLL samples, BV6 induces cell death independently of caspase activity, receptor-interacting protein (RIP)1 activity or tumor necrosis factor (TNF)a, as zVAD.fmk, necrostatin-1 or TNFa-blocking antibody Enbrel fail to inhibit cell death. Together, these novel insights into BV6-regulated cell death in CLL have important implications for developing new therapeutic strategies to overcome cell death resistance especially in poor prognostic CLL subgroups.Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the Western world. 1 Key prognostic factors besides the Rai and Binet stage are chromosomal aberrations like 17p or 11q deletion, TP53 mutation and immunoglobulin heavy-chain variable region gene (IGVH) mutation status. Although individualized therapeutic strategies have been developed, the disease is still incurable. Especially patients with 17p deletion and TP53 mutation have a very poor prognosis. 2 Therefore, new therapeutic targets that act independently of functional p53 in CLL are needed.CLL is characterized by the accumulation of Blymphocytes which has been largely attributed to defective cell death pathways rather than to aberrant proliferation. [3][4][5] Apoptosis represents one of the key forms of programmed cell death. 6 Necroptosis is a caspase-independent mode of programmed cell death that typically occurs when essential factors of apoptosis such as caspases are inhibited and is regulated by RIP1 and RIP3. 7 Inhibitor of apoptosis (IAP) proteins are major regulators of cell death and survival processes. X-linked inhibitor of apoptosis (XIAP) acts as direct caspase inhibitor, 8 while cIAP1 and -2 were shown to protect cells from cell death by acting primarily as E3 ubiquitin liga...

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Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Cited by 2,204 publications

References 182 publications

Podocyte Mitosis – A Catastrophe

Podocyte Mitosis – A Catastrophe

NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis

Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia

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