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 language | English |
|---|---|
| Pages (from-to) | 1823-1830 |
| Number of pages | 8 |
| Journal | Molecular Cancer Therapeutics |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Gam1-associated alterations of drug responsiveness through activation of apoptosis
AU - Wu, Fangting
AU - Chiocca, Susanna
AU - Beck, William T.
AU - Mo, Yin Yuan
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-06-0771
DO - 10.1158/1535-7163.MCT-06-0771
M3 - Article
C2 - 17575111
AN - SCOPUS:34250771133
VL - 6
SP - 1823
EP - 1830
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 6
ER -