Proteins associated with the promyelocytic leukemia gene product (PML)-containing nuclear body move to the nucleolus upon inhibition of proteasome-dependent protein degradation.
Several recent findings have indicated that the promyelocytic leukemia gene product (PML) oncogenic domains (PODs) are involved in proteasome-mediated degradation of ubiquitinated proteins. We wanted to examine the intracellular distribution of PML protein in the presence of a proteasome inhibitor. We used high-resolution microscopy to study the distribution of PML protein and other POD-associated proteins along with the proteasomes themselves under normal conditions and in cells treated with the proteasome inhibitor, MG132. Inhibition of the proteasomes in MCF-7, HeLa, and IB-4 cell lines resulted in a radical redistribution of the POD-associated proteins PML, Sp100, and SUMO-1. After 6-10 h of MG132 treatment, PML, Sp100, and SUMO-1 were no longer detectable in the PODs and accumulated mainly in the nucleolus. Moreover, MG132 treatment changed the cellular distribution of the proteasomes. Interestingly, this included the accumulation in euchromatin areas of the nucleus and within the nucleoli. Several non-POD-associated proteins did not change their cellular distribution under the same conditions. The accumulation of POD-associated proteins and proteasomes in the nucleoli of MG132-treated cells indicates that these proteins may target the nucleoli under normal conditions and that the nucleolus may have a function in the regulation of proteasomal protein degradation.
Mattsson
K
K
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Pokrovskaja
K
K
Kiss
C
C
Klein
G
G
Szekely
L
L
D001943:Breast Neoplasms; D002466:Cell Nucleolus / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins / Q000378:metabolism
D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C070576:PML protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex