FLICE-Inhibitory Proteins: Regulators of Death Receptor-Mediated Apoptosis

Krueger, Andreas; Baumann, Sven; Krammer, Peter H.; Kirchhoff, Sabine

doi:10.1128/mcb.21.24.8247-8254.2001

Cited by 499 publications

(434 citation statements)

References 87 publications

Supporting

Mentioning

421

Contrasting

Unclassified

Order By: Relevance

“…Resistance towards CD95-mediated apoptosis can be achieved by a number of different mechanisms or a combination thereof, such as reduced CD95 surface expression, elevated expression of c-FLIP [34] or elevated expression of anti-apoptotic Bcl-2 family members, which however, only block CD95-mediated apoptosis in type II cells that are dependent on the mitochondrial apoptotic pathway for signal amplifica- tion [9]. First, we addressed the mechanism of apoptosis resistance of LTC by analyzing CD95 surface expression levels at different time points (Fig.…”

Section: Reduced Disc Activity Of Ltc After Cd95 Stimulationmentioning

confidence: 99%

“…5B), suggesting that the strong DISC activity in day 6 cells, but not the low DISC activity in LTC, is sufficient to overcome this protection by high expression of anti-apoptotic Bcl-2 family members in day 6 cells. c-FLIP is a potent inhibitor of CD95-mediated apoptosis, which acts at the DISC level [15,34,36] through inhibition of caspase-8 activation [37]. Increased expression predominantly of the short splice variant of c-FLIP, c-FLIP S , has been suggested to contribute partially to CD95 resistance of freshly activated day 1 T cells, upon costimulation and upon restimulation of day 6 T cells [38][39][40].…”

Section: Reduced Mitochondrial Depolarization In Ltc After Cd95 Triggmentioning

confidence: 99%

See 1 more Smart Citation

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

et al. 2006

Self Cite

View full text Add to dashboard Cite

An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These longterm cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x L and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.

show abstract

Section: Reduced Disc Activity Of Ltc After Cd95 Stimulationmentioning

confidence: 99%

Section: Reduced Mitochondrial Depolarization In Ltc After Cd95 Triggmentioning

confidence: 99%

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…The first step induced by activation of death receptors is the recruitment of a complex of different proteins termed DISC (death-inducing signaling com-plex) to the intracellular death domain of these receptors through the adapter FADD (15). DISC formation results in the homodimerization and proteolytic activation of caspase 8, and this step is counterbalanced by the parallel recruitment of FLICE-inhibitory protein (FLIP), which hetero-oligomerizes with caspase 8 and reduces its proteolytic activation (16,17). Caspase 8 may induce apoptosis in RA FLS through direct activation of terminal caspases or by prior activation of caspase 9 through the mitochondrial apoptotic pathway.…”

Section: Objective Hyperplasia Of Fibroblast-like Synoviocytes (Fls)mentioning

confidence: 99%

Down‐regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas‐mediated apoptosis

Palao¹,

Santiago²,

Galindo³

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Two splice variants, termed cFLIP-a (cFLIP-long, MW B55 kD) and cFLIP-d (cFLIP-short, MW 25 to 28 kD), are the most widely distributed and well studied isoforms (Irmler et al, 1997;Krueger et al, 2001;Micheau, 2003;Rasper et al, 1998). These proteins inhibit cell death by competing with procaspase-8 for binding to FADD and inhibiting assembly of a functional DISC (Rasper et al, 1998;Scaffidi et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Expression of Cellular FLICE Inhibitory Proteins (cFLIP) in Normal and Traumatic Murine and Human Cerebral Cortex

Hainsworth

Bermpohl

Webb

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Cellular Fas-associated death domain-like interleukin-1-beta converting enzyme (FLICE) inhibitory proteins (cFLIPs) are endogenous caspase homologues that inhibit programmed cell death. We hypothesized that cFLIPs are differentially expressed in response to traumatic brain injury (TBI). cFLIP-alpha and cFLIP-delta mRNA were expressed in normal mouse brain-specifically cFLIP-delta (but not cFLIP-alpha) protein was robustly expressed. After controlled cortical impact (CCI), cFLIPalpha expression increased initially then decreased to control levels at 12 h, increasing again at 24-72 h (Po0.05). cFLIP-delta expression was decreased in brain homogenates by 12 h after CCI, then increased again at 24 to 72 h (Po0.05). cFLIP-delta immunostaining was markedly reduced in injured cortex, but not hippocampus, at 3 to 72 h after CCI. In cortex, reduced cFLIP-delta staining was found in TUNEL-positive cells, but in hippocampus TUNEL-positive cells expressed cFLIP-delta immunoreactivity. cFLIP-delta was increased in a subset of reactive astrocytes in pericontusional cortex and hippocampus at 48 to 72 h. Low levels of both cFLIP isoforms were detected in human cortical tissue with no TBI, from four patients undergoing brain surgery for epilepsy and o24 h post mortem from three patients without CNS pathologic assessment. In cortical tissue surgically removed o18 h after severe TBI (n ¼ 3), cFLIP-alpha expression was increased relative to epilepsy controls (Po0.05) but not relative to post-mortem controls. The data suggest differential spatial and temporal regulation of cFLIP-alpha and cFLIP-delta expression that may influence the magnitude of cell death and further implicate programmed mechanisms of cell death after TBI.

show abstract

FLICE-Inhibitory Proteins: Regulators of Death Receptor-Mediated Apoptosis

Cited by 499 publications

References 87 publications

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

Down‐regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas‐mediated apoptosis

Expression of Cellular FLICE Inhibitory Proteins (cFLIP) in Normal and Traumatic Murine and Human Cerebral Cortex

Contact Info

Product

Resources

About