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Cell Death Differ
2014[Nov]; 21
(11
): 1667-76
PMID25146924
show ga
Programmed cell death, a physiologic process for removing cells, is critically
important in normal development and for elimination of damaged cells. Conversely,
unattended cell death contributes to a variety of human disease pathogenesis.
Thus, precise understanding of molecular mechanisms underlying control of cell
death is important and relevant to public health. Recent studies emphasize that
transforming growth factor-?-activated kinase 1 (TAK1) is a central regulator of
cell death and is activated through a diverse set of intra- and extracellular
stimuli. The physiologic importance of TAK1 and TAK1-binding proteins in cell
survival and death has been demonstrated using a number of genetically engineered
mice. These studies uncover an indispensable role of TAK1 and its binding
proteins for maintenance of cell viability and tissue homeostasis in a variety of
organs. TAK1 is known to control cell viability and inflammation through
activating downstream effectors such as NF-?B and mitogen-activated protein
kinases (MAPKs). It is also emerging that TAK1 regulates cell survival not solely
through NF-?B but also through NF-?B-independent pathways such as oxidative
stress and receptor-interacting protein kinase 1 (RIPK1) kinase
activity-dependent pathway. Moreover, recent studies have identified TAK1's
seemingly paradoxical role to induce programmed necrosis, also referred to as
necroptosis. This review summarizes the consequences of TAK1 deficiency in
different cell and tissue types from the perspective of cell death and also
focuses on the mechanism by which TAK1 complex inhibits or promotes programmed
cell death. This review serves to synthesize our current understanding of TAK1 in
cell survival and death to identify promising directions for future research and
TAK1's potential relevance to human disease pathogenesis.
|*Cell Death
[MESH]
|Animals
[MESH]
|Apoptosis/physiology
[MESH]
|Cell Survival
[MESH]
|Homeostasis
[MESH]
|Humans
[MESH]
|MAP Kinase Kinase Kinases/*metabolism
[MESH]
|Mice
[MESH]
|Mitogen-Activated Protein Kinases/metabolism
[MESH]
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