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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
p33(ING1) enhances UVB-induced apoptosis in melanoma cells
1Division of Dermatology, Department of Medicine, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, V6H 3Z6, Canada.
Abstract:
The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells.
Insights
The tumor suppressor ING1 protein (p33ING1) promotes UV-induced apoptosis in melanoma cells. This process requires p53 and involves the mitochondrial pathway, highlighting a potential therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The ING1 tumor suppressor shares functions with p53, including mediating apoptosis.
- ING1 isoforms, like p33ING1, translocate to the nucleus and interact with PCNA after UV exposure.
Purpose of the Study:
- To investigate the role of p33ING1 in UV-induced apoptosis in melanoma cells.
- To elucidate the mechanism by which p33ING1 influences UVB-induced cell death.
Main Methods:
- Overexpression and antisense plasmid introduction of p33ING1 in melanoma cells.
- Assessment of apoptosis rates following UVB irradiation.
- Analysis of p53 dependence, Bax expression, and mitochondrial membrane potential.
Main Results:
- Overexpression of p33ING1 increased UVB-induced apoptosis, while antisense inhibition reduced it.
- p33ING1-mediated apoptosis enhancement was dependent on the presence of p53.
- p33ING1 upregulated Bax expression and altered mitochondrial membrane potential.
Conclusions:
- p33ING1 acts as a mediator of UVB-induced apoptosis in melanoma.
- p33ING1 cooperates with p53 through the mitochondrial cell death pathway in response to UVB.
- These findings suggest p33ING1 as a potential target for melanoma treatment.
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