Biomedical subjects

C R Goding

Publications and source records attributed to C R Goding.

43 records · Page 3Linked to original sources

PubMed1987

Multiple transcription factors interact with the adenovirus-2 EII-late promoter: evidence for a novel CCAAT recognition factor.

Multiple cellular transcription factors have been shown to interact with the upstream region of the adenovirus-2 EIIa-late promoter. One of these factors recognises each of the three CCAAT motifs present in the EIIL promoter at positions -72, -135 and -229, as well as the CCAAT elements in the rat albumin and herpes virus thymidine kinase promoters. A mutation known to reduce thymidine kinase promoter activity in vivo and in vitro abolishes binding of the factor, termed CCAAT recognition factor (CRF), which appears to be distinct from previously identified CCAAT factors. In addition, another protein, termed upstream factor II (USFII), shares binding sites at position -110 in the EIIL promoter and in the c-fos enhancer adjacent to the serum regulatable element. The recognition site for USFII is also found in the c-fos promoter and in the adenovirus early region EIV and EIIa-early promoters. An Sp1 recognition site has also been identified at position -41, and the binding sites for Sp1, USFII and CRF are all required for efficient EIIa-late promoter function. Finally, an additional factor recognising the consensus GGGGGGNT has been detected.

Adenovirus Early Proteins↗

PubMed1987

Mutational analysis of the adenovirus E1a gene: the role of transcriptional regulation in transformation.

To determine whether the transcription regulatory activities of the adenoviral E1a gene play a role in its ability to transform primary cells we have constructed an extensive series of mutations within the E1a gene. The mutants have been characterized for their ability to transactivate the adenoviral early promoters, repress the transcriptional stimulation of the polyoma virus enhancer, establish primary baby rat kidney cells in culture and cooperate with the activated Ha-ras oncogene in morphologically transforming these cells. The mutant phenotypes reveal that: (i) the two transcription regulatory activities of E1a are separable since essential protein domains map within different regions of the protein; (ii) transactivation is unlikely to contribute significantly to E1a-mediated transformation since several isolated mutants lost the ability to transactivate but were nevertheless efficient at transformation; and (iii) both establishment and oncogene cooperation are linked to enhancer repression suggesting that E1a transforms cells by the repression of a cellular enhancer.

Adenoviridae↗

PubMed1984

Individual products of the adenovirus 12S and 13S EIa mRNAs stimulate viral EIIa and EIII expression at the transcriptional level.

Recombinant plasmids containing mutant or wild-type adenovirus serotype 2 EIa genes that produce the 12S mRNA alone, the 13S mRNA alone, or both mRNAs were cotransfected into HeLa cells with plasmids containing the viral EIIa or EIII transcription units. The amount of RNA produced from the EIIa and EIII promoters was increased by the products of both the 13S and the 12S RNAs. By measuring the level of specific transcription in nuclei isolated from transfected cells we directly demonstrate that the increased amount of EIIa RNA is due to stimulation of the rate of transcription.

Adenoviridae↗

PubMed1983

S1 sensitive sites in adenovirus DNA.

S1 nuclease has been used as a probe for regions of DNA secondary structure in supercoiled recombinant plasmids containing adenovirus (Ad) DNA sequences. In the sequences examined two S1 sensitive sites were identified in the left-terminal 16.5% of Ad 12 DNA, one of which aligned approximately with an inverted repeat region in the DNA sequence. In addition an S1 sensitive site was dictated by a potential cruciform structure in the region of the Ad 2 major late promoter. In contrast to the expected cleavage site at the loop of the cruciform, cleavage occurred at the base of the stem in the region of the TATA box. All three S1 sensitive sites identified were more sensitive to S1 than the endogenous sites in the parent plasmids.

Adenoviridae↗

PubMed1983

Adenovirus cores can function as templates in in vitro DNA replication.

Adenovirus cores prepared by gentle disruption of virus by heating at 56 degrees C in the presence of deoxycholate were able to function as templates in an in vitro DNA replication system, allowing both initiation, indicated by the formation of terminal protein-dCMP complex, and elongation of > 300 nucleotides. Using both cores and DNA-protein complexes as templates, it was also demonstrated that novobiocin, an inhibitor of DNA gyrase, inhibited in vitro DNA replication by preventing formation of the initiation complex.

Adenoviruses, Human↗

PubMed1983

ADP-ribosylation in in vitro systems synthesizing adenovirus DNA.

Two systems utilizing extracts derived from nuclei of adenovirus-infected cells which synthesize adenovirus DNA in vitro were analysed for indications of ADP-ribosylation of virus proteins. On incubation with [32P]NAD or [14C]NAD, modification of the adenovirus T antigen could be demonstrated in one of these systems. ADP-ribosylation of adenovirus core proteins V and VII could also be demonstrated with both nuclear extracts. However, using 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) polymerase, there was no evidence either in vivo or in vitro that ADP-ribosylation played a critical role in the replication process.

Adenosine Diphosphate Ribose↗

PubMedDate not supplied

Melanocyte development and malignant melanoma.

Malignant melanoma is a notoriously aggressive disease that can affect relatively young individuals and whose incidence is rising at an alarming rate. Unlike many cancers, metastatic melanoma is poorly responsive to current therapies and mutations affecting p53, the retinoblastoma gene product or Ras which occur frequently in many other cancer types, appear to be rare or at least relatively late events in the progression of the disease. Recent advances in our understanding of the disease at the molecular level have indicated that in addition to the loss of cell cycle checkpoints which may be common to all cancers, malignant melanoma shares many characteristics in common with developmental precursors to melanocytes, the mature pigment producing cells of the skin and hair follicles which are responsible for skin and hair colour. This review therefore focuses on the signalling pathways that play a crucial role in the development of the melanocyte lineage which are subject to deregulation in malignant melanoma namely signalling by receptor tyrosine kinases, the Wnt signalling pathway, as well as loss of the p16INK4a cyclin-dependent kinase inhibitor. Intriguingly all three pathways impact on the expression or function of the microphthalmia-associated transcription factor which plays an essential role in melanocyte development.

Animals↗