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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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SERPINA3: Stimulator or Inhibitor of Pathological Changes.

Mateusz de Mezer1, Jan Rogaliński1, Stanisław Przewoźny1

  • 1Department of Immunobiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland.

Biomedicines
|January 21, 2023
PubMed
Summary

SERPINA3, an acute-phase protein, normally aids anti-inflammatory and antiviral responses. However, its dysregulation is linked to diseases like cancer and neurodegeneration, acting as a "fifth column" in disease progression.

Keywords:
DNA bindingMAPK/ERK 1/2PI3K/AKTSERPINA3anti-inflammatoryantiapoptoticα-1-antichymotrypsin

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Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • SERPINA3 (α-1-antichymotrypsin) is a plasma serine protease inhibitor involved in inflammation.
  • Elevated SERPINA3 is observed in heart failure, neurodegenerative diseases (Alzheimer's, Creutzfeldt-Jakob), and various cancers.
  • The protein's role in cancer involves antiapoptotic functions via PI3K/AKT and MAPK/ERK signaling pathways.

Purpose of the Study:

  • To summarize the known functions of SERPINA3.
  • To elucidate SERPINA3's mechanisms of action, particularly in non-cancerous diseases.
  • To highlight SERPINA3's dual role as a defense protein and a contributor to disease pathology.

Main Methods:

  • Literature review of existing studies on SERPINA3.
  • Analysis of research on SERPINA3's involvement in inflammation, viral response, and disease.
  • Focus on mechanisms beyond cancerogenesis.

Main Results:

  • SERPINA3 functions as an acute-phase protein in innate immunity.
  • Dysregulated SERPINA3 expression is implicated in diverse pathologies, including cancer and neurological disorders.
  • The protein's signaling pathways (PI3K/AKT, MAPK/ERK) contribute to its pro-survival and potentially pro-cancer effects.

Conclusions:

  • SERPINA3 has a complex role, acting as a crucial part of the defense system.
  • Aberrant SERPINA3 function can promote disease development, acting as a 'fifth column'.
  • Further research is needed to fully understand SERPINA3's mechanisms in various diseases.