title: Gam1-associated alterations of drug responsiveness through activation of apoptosis.
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.
authors.affiliation: Department of Medical Microbiology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Fangting
authors.initials: F
authors.lastname: Wu
authors.forename: Susanna
authors.initials: S
authors.lastname: Chiocca
authors.forename: William T
authors.initials: WT
authors.lastname: Beck
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D004249:DNA Damage; D017931:DNA Primers; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D014764:Viral Proteins; D053148:Caspase 3