How does caspase-1 cause apoptosis?

Pyroptosis is triggered by Caspase-1 after its activation by various inflammasomes, and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms, but are dependent on different caspases, unlike oncosis.

What is cleaved caspase-1?

Caspase-1 cleaves inflammatory cytokines such as pro-IL-1ß and interferon-γ inducing factor (IL-18) into their mature forms (1,2). Like other caspases, caspase-1 is proteolytically activated from a proenzyme to produce a tetramer of its two active subunits, p20 and p10.

Is caspase-1 a protein?

Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity.

What releases caspase?

Active caspase 1 is released from THP1 cells upon LPS/ATP stimulation. A) WEHD-afc cleavage in untreated or LPS/ATP treated cell lysates and supernatant (2×107 cells/ml) in the presence or absence of YVAD-cmk inhibitor (50 μM).

What do Gasdermin pores do?

While induction of cell death has been assumed to be the main function of the gasdermin pores, increasing evidence suggests that these pores have non-lytic functions, such as in releasing cytokines or alarmins and in regulating intracellular signaling via ionic fluxes.

Is caspase-1 a transcription factor?

A prime candidate for the transcriptional regulator of caspase-1 is the transcription factor nuclear factor-kappa B (NFκB), a well-known mediator of the inflammatory response (Karin, 2009). This dimeric complex is sequestered in the cytosol via its association with IκB.

What does the Inflammasome do?

The inflammasomes are innate immune system receptors/sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. It has been implicated in a host of inflammatory disorders.

Are caspases transcription factors?

Sp1 is a ubiquitous transcription factor that regulates many genes involved in apoptosis and senescence. Sp1 also has a role in the DNA damage response; at low levels of DNA damage, Sp1 is phosphorylated by ATM and localizes to double-strand break sites where it facilitates DNA double-strand-break repair.

Is caspase-9 an initiator?

Caspase-9, the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, is activated on the apoptosome complex, and failure to activate caspase-9 has profound pathophysiological consequences.