000116320 001__ 116320
000116320 005__ 20181203021057.0
000116320 0247_ $$2doi$$a10.1093/carcin/14.12.2447
000116320 037__ $$aARTICLE
000116320 245__ $$aDifferent stability of AP1 proteins in human keratinocyte and fibroblast cells: possible role in the cell-type specific expression of human papillomavirus type 18 genes
000116320 269__ $$a1993
000116320 260__ $$c1993
000116320 336__ $$aJournal Articles
000116320 500__ $$aSwiss Institute for Experimental Cancer Research (ISREC), Epalinges.
000116320 520__ $$aHuman papillomaviruses (HPV) replicate in keratinocyte but not fibroblast cells. Several factors, including AP1 (Jun/Fos), contribute to the cell-type specific transcription of HPV genes. The binding of AP1 upstream of the HPV type 18 early gene E6 is essential for transcription of the early genes. Here we show that AP1 levels are low in early passage human fibroblast extracts. In contrast, human keratinocyte extracts contain high levels of AP1. In agreement with this, in vivo an AP1-dependent promoter is more active in keratinocytes than in fibroblasts. Pulse chase experiments indicated that Jun and Fos are relatively stable in human keratinocyte cells after serum induction, whereas in early passage human fibroblasts they are rapidly broken down. Nuclear extracts of these fibroblasts contain a cysteine proteinase which can degrade AP1. Furthermore, the activity of a cathepsin B-like cysteine proteinase is elevated in these human fibroblast extracts relative to other cell types. Interestingly, after several passages in culture the fibroblasts lose this proteinase activity and the amount of AP1 increases. Taken together, these results suggest that the quantitative difference in AP1 proteins between human keratinocytes and fibroblasts is due to a difference in protein stability. The cathepsin B-like cysteine proteinase is a candidate for a role in the unusually rapid breakdown of AP1 in early passage human fibroblast cells. Low levels of AP1 in the fibroblasts correlate with the low activity of AP1-dependent promoters, like that of HPV-18, in these cells.
000116320 700__ $$aOfford, E. A.
000116320 700__ $$aChappuis, P. O.
000116320 700__ $$0243602$$aBeard, P.$$g169405
000116320 773__ $$j14$$k12$$q2447-55$$tCarcinogenesis
000116320 909C0 $$0252243$$pGR-BEARD$$xU11778
000116320 909CO $$ooai:infoscience.tind.io:116320$$pSV$$particle
000116320 937__ $$aGR-BEARD-ARTICLE-1993-001
000116320 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000116320 980__ $$aARTICLE