ASK-1

ASK1 (Apoptosis signal-regulating kinase 1) is a protein that in humans is encoded by the MAP3K5 gene. ASK1 is a member of the MAP kinase kinase kinase (MAP3K) family, which is involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development.

Function

ASK1 is a MAP kinase kinase kinase (MAP3K) that is activated by various molecules and cellular processes such as reactive oxygen species, endoplasmic reticulum stress, calcium influx, and growth factors. Once activated, ASK1 can phosphorylate and activate MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate JNK and p38 MAPKs. The signal transduction cascade mediated by ASK1 is involved in various cellular processes including apoptosis, cell differentiation, cell proliferation, and inflammatory response.

Clinical significance

Alterations in the ASK1 signaling pathway have been implicated in a variety of diseases including cancer, neurodegenerative diseases, cardiovascular diseases, and inflammatory diseases. In cancer, ASK1 has been shown to play a role in tumor suppression by inducing apoptosis in response to oncogenic stress. In neurodegenerative diseases, ASK1-mediated activation of JNK and p38 MAPKs has been linked to neuronal cell death. In cardiovascular diseases, ASK1 activation has been associated with cardiac hypertrophy, heart failure, and atherosclerosis. In inflammatory diseases, ASK1 has been implicated in the production of pro-inflammatory cytokines and the regulation of immune response.

See also

• Mitogen-activated protein kinase kinase kinase
• Apoptosis
• MAP kinase

References

ASK-1 Resources
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