Signals in hepatitis A virus P3 region proteins recognized by the ubiquitin-mediated proteolytic system.
The hepatitis A virus 3C protease and 3D RNA polymerase are present in low concentrations in infected cells. The 3C protease was previously shown to be rapidly degraded by the ubiquitin/26S proteasome system and we present evidence here that the 3D polymerase is also subject to ubiquitination-mediated proteolysis. Our results show that the sequence (32)LGVKDDWLLV(41) in the 3C protease serves as a protein destruction signal recognized by the ubiquitin-protein ligase E3alpha and that the destruction signal for the RNA polymerase does not require the carboxyl-terminal 137 amino acids. Both the viral 3ABCD polyprotein and the 3CD diprotein were also found to be substrates for ubiquitin-mediated proteolysis. Attempts to determine if the 3C protease or the 3D polymerase destruction signals trigger the ubiquitination and degradation of these precursors yielded evidence suggesting, but not unequivocally proving, that the recognition of the 3D polymerase by the ubiquitin system is responsible.
Losick
Vicki P
VP
Department of Chemistry, Bates College, Lewiston, ME 04240, USA.
Schlax
Peter E
PE
Emmons
Rebecca A
RA
Lawson
T Glen
TG
D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D000818:Animals; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D030041:Hepatitis A virus / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism; D020815:Polyproteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011498:Protein Precursors / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes; D015398:Signal Transduction; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D020815:Polyproteins; D011498:Protein Precursors; D025801:Ubiquitin; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease