Gam1-associated alterations of drug responsiveness through activation of apoptosis

Fangting Wu, Susanna Chiocca, William T. Beck, Yin Yuan Mo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

An early gene product, Gam1, encoded by the avian adenovirus CELO, is an inhibitory protein for the sumoylation machinery, which has been implicated in regulating a variety of cellular pathways. In this study, we found that Gam1 effectively suppressed both constitutive and inducible sumoylation and caused significant cell growth inhibition. This Gam1-mediated cell growth inhibition was associated with induction of apoptosis. In particular, Gam1 induced caspase-3 activity as detected by immunostaining and Western blot. Of interest, like the Ubc9 dominant-negative mutant, Gam1 also sensitized cells to DNA-damaging agents such as topotecan and doxorubicin and non-DNA-damaging agents such as paclitaxel and vincristine. Taken together, our findings suggest that activation of the caspase pathways is at least in part responsible for the increased apoptosis in Gam1-expressing cells and, thus, contributes to the growth inhibition and enhanced chemosensitivity.

Original languageEnglish
Pages (from-to)1823-1830
Number of pages8
JournalMolecular Cancer Therapeutics
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 1 2007

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Apoptosis
Sumoylation
Pharmaceutical Preparations
Aviadenovirus
Growth
Topotecan
Vincristine
Caspases
Paclitaxel
Caspase 3
Western Blotting
DNA
Genes
Proteins
doxorubicin-DNA

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Gam1-associated alterations of drug responsiveness through activation of apoptosis. / Wu, Fangting; Chiocca, Susanna; Beck, William T.; Mo, Yin Yuan.

In: Molecular Cancer Therapeutics, Vol. 6, No. 6, 01.06.2007, p. 1823-1830.

Research output: Contribution to journalArticle

Wu, Fangting ; Chiocca, Susanna ; Beck, William T. ; Mo, Yin Yuan. / Gam1-associated alterations of drug responsiveness through activation of apoptosis. In: Molecular Cancer Therapeutics. 2007 ; Vol. 6, No. 6. pp. 1823-1830.
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