Apoptosis signaling by death receptors

• Death receptors have been recently identified as a subgroup of the TNF-receptor superfamily with a predominant function in induction of apoptosis. The receptors are characterized by an intracellular region, called the death domain, which is required for the transmission of the cytotoxic signal. Currently, five different such death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF-receptor-related apoptosis-mediated protein (TRAMP) and TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2. The signaling pathways by which these receptors induce apoptosis are rather similar. Ligand binding induces receptor oligomerization, followed by the recruitment of an adaptor protein to the death domain through homophilic interaction. The adaptor protein then binds a proximal caspase, thereby connecting receptor signaling to the apoptotic effector machinery. In addition, further pathways have been linked to death receptor-mediated apoptosis, such as sphingomyelinases, JNK kinases and oxidative stress. These pro-apoptotic signals are counteracted by several mechanisms which inhibit apoptosis at different levels. This review summarizes the current and rapidly expanding knowledge about the biological functions of death receptors and the mechanisms to trigger or to counteract cell death.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Keyword

activation-induced apoptosis

Apoptosis

Bcl-2

caspase

CD95 (APO-1/Fas)

crma-inhibitable protease

death receptor

domain-containing receptor

fas-mediated apoptosis

inhibitor of apoptosis protein

interleukin-1-beta converting-enzyme

nf-kappa-b

nuclear factor-kappa B

programmed cell-death

systemic lupus-erythematosus

tumor-necrosis factor

tumor-necrosis-factor

tumor-necrosis-factor-related apoptosis-inducing ligand tumor-necrosis-factor-receptor-related apoptosis-mediating protein

zinc-finger protein

Publication and Content Type

ref (subject category)

art (subject category)