The promyelocytic leukemia nuclear body: sites of activity?
The promyelocytic leukemia (PML) nuclear body is one of many subnuclear domains in the eukaryotic cell nucleus. It has received much attention in the past few years because it accumulates the promyelocytic leukemia protein called PML. This protein is implicated in many nuclear events and is found as a fusion with the retinoic acid receptor RARalpha in leukemic cells. The importance of PML bodies in cell differentiation and growth is implicated in acute promyelocitic leukemia cells, which do not contain PML bodies. Treatment of patients with drugs that reverse the disease phenotype also causes PML bodies to reform. In this review, we discuss the structure, composition, and dynamics that may provide insights into the function of PML bodies. We also discuss the repsonse of PML bodies to cellular stresses, such as virus infection and heat shock. We interpret the changes that occur as evidence for a role of these structures in gene transcription. We also examine the role of the posttranslational modification. SUMO-1 addition, in directing proteins to this nuclear body. Characterization of the mobility of PML body associated proteins further supports a role in specific nuclear events, rather than the bodies resulting from random accumulations of proteins.
Programme in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Christopher H
CH
Eskiw
David P
DP
Bazett-Jones
D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D002479:Inclusion Bodies / Q000502:physiology* / Q000648:ultrastructure; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human