Premium
Targeted degradation of the retinoblastoma protein by human papillomavirus E7‐E6 fusion proteins.
Author(s) -
Scheffner M.,
Münger K.,
Huibregtse J.M.,
Howley P.M.
Publication year - 1992
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1992.tb05307.x
Subject(s) - biology , oncogene proteins , fusion protein , human papillomavirus , retinoblastoma , retinoblastoma protein , virology , protein degradation , genetics , papillomaviridae , cancer research , microbiology and biotechnology , gene , cancer , regulation of gene expression , cervical cancer , recombinant dna , cell cycle , medicine
The E6 and the E7 proteins of the oncogenic human papillomavirus types 16 and 18 can stably associate with p53 and the retinoblastoma protein, respectively. The E6‐p53 interaction results in the accelerated degradation of p53 in vitro via the ubiquitin‐dependent proteolysis system. In this study we demonstrate that a fusion protein consisting of the N‐terminal half of the HPV‐16 E7 protein and the full length HPV‐16 E6 protein promotes the in vitro degradation of the retinoblastoma protein. This indicates that the property of the HPV‐16 E6 protein to stimulate the degradation of p53 can be targeted to other proteins. Unlike the HPV‐16 or HPV‐18 E6 protein, the E6 proteins of HPV‐6 and 11 do not bind to p53 and consequently do not target p53 for degradation. Analogous E7‐E6 fusion proteins using the E6 proteins of HPV‐6 and HPV‐11, however, also have the ability to promote the degradation of the retinoblastoma protein, indicating that the property to target associated proteins for degradation is shared by the anogenital specific HPV E6 proteins.