Proteins of the PIAS family enhance the sumoylation of the papillomavirus E1 protein.
Sumoylation of the papillomavirus (PV) origin binding helicase E1 protein is critical for its function. Consequently, factors modulating the sumoylation of E1 could ultimately alter the outcome of a papillomavirus infection. We investigated the role played by phosphorylation and two known SUMO E3 ligases, RanBP2 and PIAS proteins, on the sumoylation of E1. E1 sumoylation was unaffected by phosphorylation as both wild-type and pseudo-phosphorylation mutants of BPV E1 exhibited similar sumoylation profiles. RanBP2 bound to BPV E1, but not to HPV11 E1, and lacked sumoylation enhancing activity for either E1. In contrast, proteins of the PIAS family (except PIASy) bound to both BPV and HPV11 E1 and stimulated their sumoylation. The structural integrity of the RING finger domain of the PIAS proteins was required for their E3 SUMO ligase activity on PV E1 sumoylation but was dispensable for their PV E1 binding activity. Miz1, the PIAS protein exerting the strongest E1 sumoylation enhancing activity, favored SUMO1 versus SUMO2 as the modifier and was shown to be transcribed in a keratinocyte cell line. This study indicates PIAS proteins as possible modulators of PV E1 sumoylation during papillomavirus infections.
Rosas-Acosta
Germán
G
Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
Langereis
Martijn A
MA
Deyrieux
Adeline
A
Wilson
Van G
VG
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D027383:Papillomaviridae / Q000378:metabolism*; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D014764:Viral Proteins / Q000378:metabolism* / Q000502:physiology*
D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; C084304:E1 protein, Human papillomavirus type 11; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D014764:Viral Proteins