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

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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ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

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