Introduction About The Role and Regulation of Caspase-3 (CASP3)

NCBI ID: G836

CASP3

Introduction About The Role and Regulation of Caspase-3 (CASP3)

In corals, CASP3 is activated by an unknown sensor and pathway during invasive infection, leading to the cleavage of gasdermin E (GSDME) and subsequent induction of pyroptosis [1A].
In cancer cells, increased levels of prostate cancer antigen 3 (PC-3) can perturb zinc regulation, potentially altering basal caspase-3 activity within the cell.
During apoptosis, activated caspase-3 cleaves a small percentage of p65, generating a p65 fragment that interferes with the activation-induced nuclear translocation of RPS3. This selective inhibition of NF-kappaB anti-apoptotic transcription shifts the cellular balance towards apoptosis.
The expression of pUL138 in gastric cancer cells can inhibit caspase-3 cleavage and block the function of heat shock protein 70 (HSP70), thereby promoting apoptotic cancer cell death.
Caspase-3 activation is involved in the Phoenix Rising pathway, where it promotes programmed cell death by apoptosis and leads to the production of prostaglandin E2 (PGE2), which accelerates tumor repopulation [5A].
Caspase-3 activation is also linked to the DNA damage response (DDR) pathway, where it plays a role in determining cell fate in response to DNA damage caused by radiation [5B].

These viewpoints provide insights into the diverse roles and regulatory mechanisms of caspase-3 in various biological contexts, including coral infection, cancer progression, apoptosis, and DNA damage response.
Caspase-3, also known as caspase-3/-7, is a key protein involved in the apoptotic signaling pathway in different cell types. In Jurkat T cells, MST1 acts as a regulator of the extrinsic apoptotic pathway, and its proteolytic activation is stimulated by active ERK1/2 signaling. Caspase-8 may potentially activate MST1 in these cells, and MST1, in turn, potentiates the activation of caspase-3, -7, and -8, forming a positive feed-back loop to amplify the apoptotic signal.

In gastric cancer (GC) cells, MeCP2 inhibits apoptosis by suppressing the MYOD1/Caspase-3 signaling pathway. Knockdown of MeCP2 leads to increased expression of MYOD1 and results in the up-regulation of active Caspase-3, inducing apoptosis and inhibiting GC cell proliferation.

TFF3, when overexpressed, activates the PI3K/AKT pathway to block the mitochondria-induced apoptotic pathway in prostate tumorigenesis. Silencing TFF3 has the opposite effect, promoting the release of proapoptotic proteins from the mitochondria, activating caspase-9 and caspase-3, and inducing apoptotic cell death.

During Newcastle disease virus (NDV) infection in a chicken fibroblast cell line, knockdown of 2'-5'-oligoadenylate synthetase-like (OASL) leads to lower expression of CASP3 gene and other caspase genes. This reduction in caspase expression results in a higher level of NDV viral RNA.

Overall, caspase-3 plays a crucial role in apoptosis regulation in different cellular contexts, either as a positive regulator in the apoptotic pathway or as a target for inhibition by specific proteins. Its involvement is observed in T cells, gastric cancer cells, prostate tumorigenesis, and NDV infection.

Protein Name: Caspase 3

Functions: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:7596430, PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:7596430, PubMed:18723680, PubMed:20566630, PubMed:23650375). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:7774019, PubMed:7596430, PubMed:10497198, PubMed:16374543). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (PubMed:7596430). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35446120, PubMed:35338844). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486)

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