Low- and high-risk human papillomavirus E7 proteins regulate p130 differently.
The E7 protein of high-risk human papillomaviruses (HR HPVs) targets pRb family members (pRb, p107 and p130) for degradation; low-risk (LR) HPV E7 only targets p130 for degradation. The effect of HR HPV 16 E7 and LR HPV 6 E7 on p130 intracellular localization and half-life was examined. Nuclear/cytoplasmic fractionation and immunofluorescence showed that, in contrast to control and HPV 6 E7-expressing cells, a greater amount of p130 was present in the cytoplasm in the presence of HPV 16 E7. The half-life of p130, relative to control cells, was decreased in the cytoplasm in the presence of HPV 6 E7 or HPV 16 E7, but only decreased by HPV 6 E7 in the nucleus. Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. These results suggest that there may be divergent mechanisms by which LR and HR HPV E7 target p130 for degradation.
Barrow-Laing
Lisa
L
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Chen
Wei
W
Roman
Ann
A
D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D006207:Half-Life; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D052163:Human papillomavirus 6 / Q000472:pathogenicity*; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D050725:Papillomavirus E7 Proteins