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The promyelocytic leukemia protein PML has a pro-apoptotic activity mediated through its RING domain
K L Borden1, E J CampbellDwyer, M S Salvato
1Department of Biochemistry, Dalhousie University, Halifax, N.S., Canada. kborden@is.dal.ca
Abstract:
The promyelocytic leukemia protein PML is known to form nuclear multiprotein complexes which are compromised in several pathogenic conditions including acute promyelocytic leukemia. We show that in cells infected with a single stranded RNA virus, which relocates PML bodies to the cytoplasm, the infected cells are more resistant to serum starvation induced apoptosis than their uninfected counterparts. Antisense PML oligonucleotides increase cell survival under serum deprivation conditions indicating that PML is directly involved in the apoptotic activity. Transient transfection studies have indicated that this pro-apoptotic activity of PML is mediated through the zinc binding region known as the RING finger. Viral attack of PML nuclear bodies appears to allow the virus to deregulate host cell apoptotic machinery in order to establish chronic infection.
Insights
Promyelocytic leukemia protein (PML) promotes apoptosis. Viral infection relocates PML, enhancing cell survival against serum starvation, suggesting PML
Area of Science:
- Cell biology
- Virology
- Molecular biology
Background:
- The promyelocytic leukemia protein (PML) forms nuclear bodies crucial for cellular processes.
- PML dysfunction is implicated in diseases like acute promyelocytic leukemia.
- Viral infections can alter the localization and function of cellular proteins.
Purpose of the Study:
- To investigate the role of PML in apoptosis during viral infection.
- To determine if PML relocation affects cellular resistance to serum starvation-induced apoptosis.
- To identify the PML domain responsible for its pro-apoptotic activity.
Main Methods:
- Single-stranded RNA virus infection of cells.
- Monitoring of PML body localization (nuclear vs. cytoplasmic).
- Assessment of apoptosis resistance under serum starvation.
- Use of antisense PML oligonucleotides.
- Transient transfection studies to map functional domains.
Main Results:
- Viral infection relocated PML bodies to the cytoplasm.
- PML-relocated cells exhibited increased resistance to serum starvation-induced apoptosis.
- Antisense PML oligonucleotides enhanced cell survival during serum deprivation.
- The RING finger domain of PML was identified as mediating its pro-apoptotic function.
Conclusions:
- PML plays a pro-apoptotic role, mediated by its RING finger domain.
- Viral relocation of PML bodies contributes to enhanced cell survival.
- Viruses may exploit PML to dysregulate host apoptosis for persistent infection.