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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
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CRISPR01:59

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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Apoptosis01:30

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Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
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Caspase-8: The double-edged sword.

Ranadip Mandal1, Joan Compte Barrón2, Izabela Kostova1

  • 1Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany.

Biochimica Et Biophysica Acta. Reviews on Cancer
|March 10, 2020
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Summary
This summary is machine-generated.

Caspase-8 (CASP8) initiates apoptosis but also regulates survival pathways. While often lost in some cancers, its non-apoptotic roles offer growth advantages, making it a key therapeutic target.

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Area of Science:

  • Molecular Biology
  • Cell Death Pathways
  • Cancer Biology

Background:

  • Caspase-8 (CASP8) is a protease classically linked to extrinsic apoptosis via Death Receptors (DRs).
  • CASP8 also influences anoikis, autophagy, pyroptosis, and importantly, inhibits necroptosis, a pro-survival function.
  • Low CASP8 expression is linked to cancer, but most cancers maintain or elevate CASP8, suggesting non-apoptotic roles are critical.

Purpose of the Study:

  • To review the multifaceted roles of Caspase-8 in cellular processes.
  • To explore the clinical significance of Caspase-8 in various cancer types.
  • To discuss therapeutic strategies targeting Caspase-8 in oncology.

Main Methods:

  • Literature review of Caspase-8 functions.
  • Analysis of Caspase-8 expression and activity in cancer.
  • Examination of therapeutic approaches targeting Caspase-8.

Main Results:

  • Caspase-8 has diverse roles beyond apoptosis, including regulating cell survival and death.
  • While some cancers lose CASP8, many retain or increase it, utilizing its non-apoptotic functions for growth.
  • CASP8's complex roles present opportunities for novel anti-cancer therapies.

Conclusions:

  • Caspase-8's non-apoptotic functions are crucial for cancer cell growth and survival.
  • Targeting Caspase-8 offers a promising therapeutic avenue in oncology.
  • Understanding CASP8's dual roles is essential for effective cancer treatment strategies.