The promyelocytic leukemia protein PML has a pro-apoptotic activity mediated through its RING domain.
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.
Borden
K L
KL
Department of Biochemistry, Dalhousie University, Halifax, N.S., Canada. kborden@is.dal.ca
CampbellDwyer
E J
EJ
Salvato
M S
MS
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis; D000071156:Promyelocytic Leukemia Protein; D017510:Protein Folding; D011994:Recombinant Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D010948:Viral Plaque Assay
D016895:Culture Media, Serum-Free; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C513293:Pml protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D000071156:Promyelocytic Leukemia Protein; D011994:Recombinant Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins