Effects of the combination of a proteasome inhibitor (PSI) and an inhibitor of ubiquitin-ligases (Leu-Ala) on the ultrastructure of human leukemic U937 cells

P. Biały, H. Ziemba, E. Pleban, Cezary Wojcik

Research output: Contribution to journalArticle

Abstract

We have used the dipeptide Leu-Ala in an attempt to prevent the formation of ubiquitin-protein conjugates in U937 cells by inhibition of cellular E3 enzymes (ubiquitin ligases). Proteasome inhibitors induce the formation of perinuclear aggregates for ubiquitinated proteins and proteasomes (aggresomes) in the area of the proteolytic center of the cell. Leu-Ala did not prevent the formation of those aggregates under the action of PSI (peptidyl aldehyde, selective inhibitor of the chymotrypsin-like activity of the proteasome), however it induced an accumulation of lipid droplets in treated cells, suggesting a previously unknown involvement of Leu-Ala in lipid metabolism. We conclude, that either Leu-Ala is not able to completely inhibit the cellular E3 enzymes or some of those enzymes are insensitive to this dipeptide, allowing therefore the build-up of ubiquitin-conjugates in the proteolytic centre of the cell.

Original languageEnglish (US)
Pages (from-to)135-136
Number of pages2
JournalFolia Histochemica et Cytobiologica
Volume40
Issue number2
StatePublished - 2002
Externally publishedYes

Fingerprint

leucyl-alanine
U937 Cells
Proteasome Inhibitors
Ligases
Ubiquitin
Dipeptides
Proteasome Endopeptidase Complex
Enzymes
Ubiquitinated Proteins
Ubiquitin-Protein Ligases
Chymotrypsin
Lipid Metabolism
Aldehydes
Proteins

Keywords

  • Aggresome
  • Leukemia
  • Lipid metabolism
  • Proteasome
  • Ubiquitin
  • Ubiquitin ligase
  • Ultrastructure

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

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abstract = "We have used the dipeptide Leu-Ala in an attempt to prevent the formation of ubiquitin-protein conjugates in U937 cells by inhibition of cellular E3 enzymes (ubiquitin ligases). Proteasome inhibitors induce the formation of perinuclear aggregates for ubiquitinated proteins and proteasomes (aggresomes) in the area of the proteolytic center of the cell. Leu-Ala did not prevent the formation of those aggregates under the action of PSI (peptidyl aldehyde, selective inhibitor of the chymotrypsin-like activity of the proteasome), however it induced an accumulation of lipid droplets in treated cells, suggesting a previously unknown involvement of Leu-Ala in lipid metabolism. We conclude, that either Leu-Ala is not able to completely inhibit the cellular E3 enzymes or some of those enzymes are insensitive to this dipeptide, allowing therefore the build-up of ubiquitin-conjugates in the proteolytic centre of the cell.",
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T1 - Effects of the combination of a proteasome inhibitor (PSI) and an inhibitor of ubiquitin-ligases (Leu-Ala) on the ultrastructure of human leukemic U937 cells

AU - Biały, P.

AU - Ziemba, H.

AU - Pleban, E.

AU - Wojcik, Cezary

PY - 2002

Y1 - 2002

N2 - We have used the dipeptide Leu-Ala in an attempt to prevent the formation of ubiquitin-protein conjugates in U937 cells by inhibition of cellular E3 enzymes (ubiquitin ligases). Proteasome inhibitors induce the formation of perinuclear aggregates for ubiquitinated proteins and proteasomes (aggresomes) in the area of the proteolytic center of the cell. Leu-Ala did not prevent the formation of those aggregates under the action of PSI (peptidyl aldehyde, selective inhibitor of the chymotrypsin-like activity of the proteasome), however it induced an accumulation of lipid droplets in treated cells, suggesting a previously unknown involvement of Leu-Ala in lipid metabolism. We conclude, that either Leu-Ala is not able to completely inhibit the cellular E3 enzymes or some of those enzymes are insensitive to this dipeptide, allowing therefore the build-up of ubiquitin-conjugates in the proteolytic centre of the cell.

AB - We have used the dipeptide Leu-Ala in an attempt to prevent the formation of ubiquitin-protein conjugates in U937 cells by inhibition of cellular E3 enzymes (ubiquitin ligases). Proteasome inhibitors induce the formation of perinuclear aggregates for ubiquitinated proteins and proteasomes (aggresomes) in the area of the proteolytic center of the cell. Leu-Ala did not prevent the formation of those aggregates under the action of PSI (peptidyl aldehyde, selective inhibitor of the chymotrypsin-like activity of the proteasome), however it induced an accumulation of lipid droplets in treated cells, suggesting a previously unknown involvement of Leu-Ala in lipid metabolism. We conclude, that either Leu-Ala is not able to completely inhibit the cellular E3 enzymes or some of those enzymes are insensitive to this dipeptide, allowing therefore the build-up of ubiquitin-conjugates in the proteolytic centre of the cell.

KW - Aggresome

KW - Leukemia

KW - Lipid metabolism

KW - Proteasome

KW - Ubiquitin

KW - Ubiquitin ligase

KW - Ultrastructure

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JO - Folia Histochemica et Cytochemica

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SN - 0015-5586

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