Ubiquitylation and destruction of endogenous c-mycS by the proteasome: are myc boxes dispensable?
c-MycS proteins are truncated forms of the transcription factor which have been shown to be produced by translation initiation at internal methionines (101, 121, and 134) and to be functional in the regulation of gene expression, cell proliferation, and apoptosis. Treatment of human leukemia HL60 cells with lactacystin, a specific inhibitor of the proteasome, increased the steady-state levels of endogenous c-MycS proteins. The half-life of endogenous [(35)S]MycS was similar to that of c-Myc ( approximately 23 min) in HL60 cells. c-Myc(Delta2-143), which lacks the transcription regulatory domain, had a half-life which was similar to that of endogenous c-Myc in 293 and HL60 cells. Treatment of the cells with lactacystin stabilized [(35)S]Myc(Delta2-143) and [(35)S]Myc and caused multi-ubiquitin conjugates of c-Myc, c-MycS, and Myc(Delta2-143) to accumulate. These findings indicate that the Myc homology boxes and the rest of the transcription regulatory domain (the first 144 amino acids) are dispensable for ubiquitylation and rapid destruction of c-MycS and c-Myc by the proteasome.
Chen
L
L
Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Smith
L
L
Accavitti-Loper
M A
MA
Omura
S
S
Bingham Smith
J
J
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016259:Genes, myc; D018922:HL-60 Cells; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D014452:Ubiquitins; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine