The tumor suppressor protein p53 and the adenoviral 12 S E1A oncoprotein are both known to elicit their biological effects mainly by regulating the transcription of important cellular genes. The human proliferating cell nuclear antigen (PCNA) gene is a transcriptional target of both p53 and E1A. We have analyzed the effects of p53 and 12 S E1A, separately as well as together, on PCNA gene trans...

Proteins encoded by the adenovirus E1A gene regulate both cellular and viral genes to mediate effects on cell cycle, differentiation, and cell growth control. We have identified the mouse mammary tumor virus (MMTV) promoter as a target of E1A action and investigated the role nucleoprotein structure plays in its response to E1A. Both 12 and 13 S forms target the MMTV promoter when it has a disor...

Human adenovirus type 12 (Ad12) E1A protein (E1A-12) is the key determinant of viral tumorigenesis. E1A-12 mediates major histocompatibility complex class I (MHC-I) shutoff by inhibiting the DNA binding of the transcriptional activator NF-kappaB (p50/p65) to the class I enhancer. This enables Ad12 tumorigenic cells to avoid class I recognition and lysis by cytotoxic T lymphocytes. In this study...

The adenovirus (Ad) E1A 243R oncoprotein encodes an N-terminal transcription repression domain that is essential for early viral functions, cell immortalization, and cell transformation. The transcription repression function requires sequences within amino acids 1 to 30 and 48 to 60. To elucidate the roles of the TATA-binding protein (TBP), p300, and the CREB-binding protein (CBP) in the mechan...

Human adenovirus type 12 (Ad12) E1A protein (E1A-12) is the key determinant of viral tumorigenesis. E1A-12 mediates major histocompatibility complex class I (MHC-I) shutoff by inhibiting the DNA binding of the transcriptional activator NFB (p50/p65) to the class I enhancer. This enables Ad12 tumorigenic cells to avoid class I recognition and lysis by cytotoxic T lymphocytes. In this study, we d...

The human papillomavirus E7 gene product is an oncoprotein with properties similar to those of the adenovirus E1A proteins. The human papillomavirus E7 proteins possess substantial amino acid sequence similarity to portions of conserved regions 1 and 2 of E1A, and the human papillomavirus type 16 E7 protein trans-activates the adenovirus E2 early promoter. Analysis of point mutations in the E2 ...

Gene therapy trials in human breast, ovarian, and head and neck tumors indicate that adenovirus E1A can sensitize cancer cells to the cytotoxic effects of paclitaxel in vitro and in vivo. Resistance to paclitaxel has been reported to occur in cells expressing low levels of the Forkhead transcription factor FOXO3a. In this article, we report that FOXO3a is critical for E1A-mediated chemosensitiz...

Here, we report the identification of a new E1A binding protein complex that is essential for E1A-mediated transformation. Its core component is a SWI2/SNF2-related, 400 kDa protein (p400). Other components include the myc- and p/CAF-associated cofactor, TRRAP/PAF400, the DNA helicases TAP54alpha/beta, actin-like proteins, and the human homolog of the Drosophila Enhancer of Polycomb protein. An...

The adenovirus E1A proteins form complexes with a group of cellular proteins, including a protein of 130 kD. E1A-associated p130 was purified through coimmunoprecipitation with E1A, and sequence data from four tryptic peptides was obtained. Oligonucleotides derived from the peptide sequences were used to clone a 4.85-kb cDNA. The cDNA contained an 1139-amino-acid open reading frame with homolog...

The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiat...