Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts

Giselle Perry, Viyaya Iragavarapu-Charyulu, Edward W. Harhaj, Marta Torroella-Kouri

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Macrophages from mice bearing advanced mammary tumors are critically impaired in their immune functions, exhibiting reduced expression at the mRNA and protein levels of the crucial transcription factors, nuclear factor κB (NFκB) and CCAAT enhancer binding protein (C/EBP). We have previously shown that tumor-derived factors such as transforming growth factor ß (TGFß) and prostaglandin E2 (PGE2) modulate NFκB and C/EBP expression in macrophages. Transcriptional, post-transcriptional, translational and/or post-translational mechanisms may also play a role in altered levels of NFκB and C/EBP in macrophages from tumor hosts, contributing to impaired inflammatory response. One of the post-translational mechanisms that may tune down or recycle proteins in cells is the proteasomal pathway. Since upregulation of ubiquitin/proteasomal pathways has been described under cancer-induced cachexia, we examined the possible role of this proteolytic machinery in the decrease of NFκB and C/EBP proteins in macrophages from tumor hosts. Using MG-132 proteasome inhibitor to block the proteasome machinery in macrophages from normal and tumor-bearing animals we found that macrophages from tumor hosts display higher ubiquitination and proteolysis compared to those from normal mice and also that NFκB and C/EBP downregulation is reversed in these treated cells. Thus, proteasome degradation may contribute, at least in part, to NFκB and C/EBP impairment in macrophages from tumor-bearers.

Original languageEnglish
Pages (from-to)875-881
Number of pages7
JournalOncology Reports
Volume23
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

CCAAT-Enhancer-Binding Proteins
Proteasome Endopeptidase Complex
Transcription Factors
Down-Regulation
Macrophages
Neoplasms
Cachexia
Proteins
Proteasome Inhibitors
Ubiquitination
Transforming Growth Factors
Ubiquitin
Dinoprostone
Proteolysis
Up-Regulation
Breast Neoplasms
Messenger RNA

Keywords

  • Ccaat enhancer binding protein
  • Immune suppression
  • Macrophages
  • MG-132
  • Nuclear factor κb
  • Proteasome degradation
  • Proteasome inhibitor
  • Tumor-bearing mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts. / Perry, Giselle; Iragavarapu-Charyulu, Viyaya; Harhaj, Edward W.; Torroella-Kouri, Marta.

In: Oncology Reports, Vol. 23, No. 3, 01.03.2010, p. 875-881.

Research output: Contribution to journalArticle

Perry, Giselle ; Iragavarapu-Charyulu, Viyaya ; Harhaj, Edward W. ; Torroella-Kouri, Marta. / Role of the proteasome in the downregulation of transcription factors NFκB and C/EBP in macrophages from tumor hosts. In: Oncology Reports. 2010 ; Vol. 23, No. 3. pp. 875-881.
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