Adeno-associated virus small rep proteins are modified with at least two types of polyubiquitination.
Adeno-associated virus (AAV) type 2 and 5 proteins Rep52 and Rep40 were polyubiquitinated during AAV-adenovirus type 5 (Ad5) coinfection and during transient transfection in either the presence or absence of Ad5 E4orf6 and E1b-55k. Polyubiquitination of small Rep proteins via lysine 48 (K48) linkages, normally associated with targeting of proteins for proteasomal degradation, was detected only in the presence of E4orf6. The small Rep proteins were ubiquitinated via lysine 63 (K63) following transfection in either the presence or absence of E4orf6 or following coinfection with Ad5. E4orf6/E1b-55k-dependent K48-specific polyubiquitination of small Rep proteins could be inhibited using small interfering RNA (siRNA) to cullin 5.
Farris
K David
KD
Department of Molecular Microbiology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri 65211, USA.
Fasina
Olufemi
O
Sukhu
Loretta
L
Li
Long
L
Pintel
David J
DJ
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D017504:Adenovirus E4 Proteins; C496871:CUL5 protein, human; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D014764:Viral Proteins; C068734:rep proteins, Adeno-associated virus 2; D004265:DNA Helicases; C477740:Rep40 protein, adeno-associated virus