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Clinical and epidemiological data have implicated the human papillomaviruses (HPVs) as having an etiologic role in some anogenital malignancies, with HPV-16 being most frequently (greater than 60%) detected in cervical carcinoma. HPV-16 is actively transcribed in the cancers; the most abundant transcripts map to the E6 and E7 early open reading frames.(More)
Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable protein/protein complexes with the oncoproteins of two DNA tumor viruses, the adenovirus E1A proteins and the simian virus 40 (SV40) large T antigen. Neither of these viruses(More)
TGF-beta 1 is demonstrated to inhibit skin keratinocyte proliferation when added during the G1 phase of the cell cycle. Human foreskin keratinocytes transformed with either HPV-16 or -18 or SV40, however, were resistant to the growth inhibitory effects of TGF-beta 1. Since TGF-beta 1 appears to inhibit keratinocyte growth through down-regulation of c-myc,(More)
The potential tumor suppressor antizyme and its endogenous inhibitor (antizyme inhibitor, AZI) have been implicated in the ubiquitin-independent proteasomal degradation of proteins involved in cell proliferation as well as in the regulation of polyamine levels. We show here that both antizyme and AZI concentrate at centrosomes and that antizyme(More)
Mitochondria have emerged as central regulators of apoptosis. Here, we show that TID1, a human homolog of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2)tid, encodes two mitochondrial matrix proteins, designated hTid-1(L) and hTid-1(S). These splice variants are both highly conserved members of the DnaJ family of proteins, which(More)
The early human papillomavirus type 16 genes that directly participate in the in vitro transformation of primary human keratinocytes have been defined. In the context of the full viral genome, mutations in either the E6 or E7 open reading frame completely abrogated transformation of these cells. Mutations in the E1, E2, and E2-E4 open reading frames, on the(More)
Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as(More)
The human papillomaviruses (HPVs) associated with genital tract lesions can be classified as either "high risk" or "low risk" based on their association with human anogenital cancer. The E7 proteins of the high-risk and the low-risk viruses are quite similar in their amino acid composition and structural organization yet differ in their transforming(More)
Centrosome abnormalities are a frequent finding in various malignant tumors. Since centrosomes form the poles of the mitotic spindle, these abnormalities have been implicated in chromosome missegregation and the generation of aneuploid cells which is commonly found in many human neoplasms. It is a matter of debate, however, whether centrosome alterations(More)
The steady-state level and metabolic half-life of retinoblastoma tumor suppressor protein pRB are decreased in cells that express high-risk human papillomavirus (HPV) E7 proteins. Here we show that pRB degradation is a direct activity of E7 and does not reflect a property of cell lines acquired during the selection process for E7 expression. An(More)