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Relationship between the Expression Level of PSMD11 and Other Proteasome Proteins with the Activity of Ricin and

D V Maltseva1,2,3, M P Raigorodskaya4, O V Tikhonova5

  • 1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. dmaltseva@gmail.com.

Doklady. Biochemistry and Biophysics
|September 7, 2020
PubMed

Insights

This study reveals how proteasome proteins and ERAD system proteins affect the toxicity of ribosome-inactivating proteins like ricin and viscumin. It highlights differing proteasome roles in toxin degradation and Cdc37

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Toxicology

Background:

  • Type II ribosome-inactivating proteins (RIPs), such as ricin and viscumin, are potent toxins that inhibit protein synthesis by inactivating ribosomes.
  • The cellular mechanisms, including protein degradation pathways, that govern the cytotoxicity of these toxins are not fully understood.
  • The endoplasmic reticulum-associated degradation (ERAD) system and the proteasome are key cellular machinery involved in protein quality control and degradation.

Purpose of the Study:

  • To investigate the distinct roles of proteasome proteins and ERAD system components in the cytotoxicity of ricin and viscumin.
  • To compare the contribution of the proteasome to the degradation of the catalytic subunits of these two type II RIPs.
  • To elucidate the function of the Cdc37 co-chaperone in the cytoplasmic stability of the viscumin A subunit.

Main Methods:

  • Utilized the HT29 colorectal adenocarcinoma cell line and a derived HT29-sh002 cell line.
  • Performed proteome analysis to compare protein expression profiles between the cell lines.
  • Quantified the proportion of inactivated ribosomes to assess toxin activity and cellular response.

Main Results:

  • Proteome analysis and ribosome inactivation data indicated that the proteasome contributes differently to the degradation of the catalytic subunits of ricin and viscumin.
  • The study identified a significant role for the Cdc37 co-chaperone in maintaining the stability of the viscumin A subunit within the cytoplasm.
  • Differential involvement of proteasomal and ERAD pathways in processing these structurally related toxins was observed.

Conclusions:

  • The proteasome plays a variable role in the cellular defense against type II ribosome-inactivating proteins, depending on the specific toxin.
  • Cdc37 is crucial for the cytoplasmic persistence and potential activity of the viscumin A subunit, influencing overall toxin efficacy.
  • Targeting these protein degradation pathways could offer strategies to modulate the toxicity of RIPs like ricin and viscumin.
Keywords:
Cdc37ERADHT29MLIPSMD11degradationproteasomeribosome inactivating proteinricinviscumin

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