Author
Guillermina Lozano
Bio: Guillermina Lozano is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Mutant & Carcinogenesis. The author has an hindex of 76, co-authored 225 publications receiving 20635 citations.
Topics: Mutant, Carcinogenesis, Mdm2, Gene, Cancer
Papers published on a yearly basis
Papers
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TL;DR: Rescue of the mdm2−/− lethality in a p53 null background suggests that a critical in vivo function of MDM2 is the negative regulation of p53 activity.
Abstract: The gene p53 encodes a transcriptional activator of genes involved in growth arrest, DNA repair and apoptosis. Loss of p53 function contributes to tumour development in vivo. The transcriptional activation function of p53 is inactivated by interaction with the mdm2 gene product. Amplification of mdm2 has been observed in 36% of human sarcomas, indicating that it may represent an alternative mechanism of preventing p53 function in tumour development. To study mdm2 function in vivo, we generated an mdm2 null allele by homologous recombination. Mdm2 null mice are not viable, and further analysis revealed embryonic lethality around implantation. To examine the importance of the interaction of MDM2 with p53 in vivo, we crossed mice heterozygous for mdm2 and p53 and obtained progeny homozygous for both p53 and mdm2 null alleles. Rescue of the mdm2-/- lethality in a p53 null background suggests that a critical in vivo function of MDM2 is the negative regulation of p53 activity.
1,446 citations
TL;DR: A model is proposed whereby SNP309 serves as a rate-limiting event in carcinogenesis, and a single nucleotide polymorphism (SNP309) is found in the MDM2 promoter and is shown to increase the affinity of the transcriptional activator Sp1, resulting in higher levels ofMDM2 RNA and protein and the subsequent attenuation of the p53 pathway.
1,226 citations
TL;DR: In vivo validation for the gain-of-function properties of certain p53 missense mutations are provided and a mechanistic basis for these phenotypes is suggested.
977 citations
TL;DR: Pirh2, a gene regulated by p53 that encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity, is described and it is proposed that Pirh2 is involved in the negative regulation of p53 function through physical interaction and ubiquit in-mediated proteolysis.
735 citations
TL;DR: The protein encoded by the wild-type p53 proto-oncogene has been shown to suppress transformation, whereas certain mutations that alter p53 become transformation competent, and the inability of the p53 mutant proteins to activate transcription may enable them to be transformation competent.
Abstract: The protein encoded by the wild-type p53 proto-oncogene has been shown to suppress transformation, whereas certain mutations that alter p53 become transformation competent. Fusion proteins between p53 and the GAL4 DNA binding domain were made to anchor p53 to a DNA target sequence and to allow measurement of transcriptional activation of a reporter plasmid. The wild-type p53 stimulated transcription in this assay, but two transforming mutations in p53 were unable to act as transcriptional activators. Therefore, p53 can activate transcription, and transformation-activating mutations result in a loss of function of the p53 protein. The inability of the p53 mutant proteins to activate transcription may enable them to be transformation competent.
614 citations
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TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.
Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
33,785 citations
TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
8,339 citations
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
7,653 citations
TL;DR: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death, and the disruption of p53 has severe consequences when a highly connected node in the Internet breaks down.
Abstract: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death. As when a highly connected node in the Internet breaks down, the disruption of p53 has severe consequences.
6,605 citations
TL;DR: The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases.
Abstract: ▪ Abstract The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-κB is through interactions with an inhibitor protein called IκB. Recent evidence confirms the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. NF-κB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-κB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IκB. Exciting new research has elaborated several important and unexpected findings that...
5,833 citations