Identification of a polymorphism in the RING finger of human Bmi-1 that causes its degradation by the ubiquitin-proteasome system.
Bmi-1 is a polycomb protein that plays an important role in tumor cell development and maintaining stem cell populations of many cell lineages. Here we identify a polymorphism in human Bmi-1 that changes a cysteine within its RING domain to tyrosine. This C18Y polymorphism is associated with a significant decrease in Bmi-1 level and its elevated ubiquitination, suggesting that it is being destroyed by the ubiquitin-proteasome system. Consistent with this, treating cells with the proteasome inhibitor MG-132 significantly increases C18Y Bmi-1 levels. This is the first example of a polymorphism in Bmi-1 that reduces levels of this important protein.
Zhang
Jie
J
Graduate Center for Toxicology, Chandler Medical Center, University of Kentucky, Lexington, KY 40536, USA.
Sarge
Kevin D
KD
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011489:Protein Denaturation / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D054829:RING Finger Domains / Q000235:genetics*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014443:Tyrosine / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
C069077:BMI1 protein, human; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; D014443:Tyrosine; D063150:Polycomb Repressive Complex 1; D046988:Proteasome Endopeptidase Complex; D003545:Cysteine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde