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Biomedical subjects

R Verona

Publications and source records attributed to R Verona.

15 recordsLinked to original sources

E2f3 is critical for normal cellular proliferation.

E2F is a family of transcription factors that regulate both cellular proliferation and differentiation. To establish the role of E2F3 in vivo, we generated an E2f3 mutant mouse strain. E2F3-deficient mice arise at one-quarter of the expected frequency, demonstrating that E2F3 is important for normal development. To determine the molecular consequences of E2F3 deficiency, we analyzed the properties of embryonic fibroblasts derived from E2f3 mutant mice. Mutation of E2f3 dramatically impairs the mitogen-induced, transcriptional activation of numerous E2F-responsive genes. We have been able to identify a number of genes, including B-myb, cyclin A, cdc2, cdc6, and DHFR, whose expression is dependent on the presence of E2F3 but not E2F1. We further show that a critical threshold level of one or more of the E2F3-regulated genes determines the timing of the G(1)/S transition, the rate of DNA synthesis, and thereby the rate of cellular proliferation. Finally, we show that E2F3 is not required for cellular immortalization but is rate limiting for the proliferation of the resulting tumor cell lines. We conclude that E2F3 is critical for the transcriptional activation of genes that control the rate of proliferation of both primary and tumor cells.

Animals↗

E2F-6, a member of the E2F family that can behave as a transcriptional repressor.

The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription of genes that direct the process of cell division. All previously identified E2F proteins can act in a similar manner; depending on whether or not they are associated with the cell cycle inhibitors the retinoblastoma protein (pRB), p107, or p130, they can either repress or activate the transcription of E2F-responsive genes. We now report the cloning and characterization of another E2F family member, E2F-6, whose structure is reminiscent of the dominant inhibitors of other transcription factor families. The dimerization and DNA binding properties of E2F-6 are similar to those of the other E2F family members. However, it is not regulated by pRB, p107, or p130, and it is unable to activate transcription. Instead, it can act to repress the transcription of E2F responsive genes by countering the activity of the other E2F complexes via a pRB-, p107-, or p130-independent mechanism.

Amino Acid Sequence↗

E2F activity is regulated by cell cycle-dependent changes in subcellular localization.

E2F directs the cell cycle-dependent expression of genes that induce or regulate the cell division process. In mammalian cells, this transcriptional activity arises from the combined properties of multiple E2F-DP heterodimers. In this study, we show that the transcriptional potential of individual E2F species is dependent upon their nuclear localization. This is a constitutive property of E2F-1, -2, and -3, whereas the nuclear localization of E2F-4 is dependent upon its association with other nuclear factors. We previously showed that E2F-4 accounts for the majority of endogenous E2F species. We now show that the subcellular localization of E2F-4 is regulated in a cell cycle-dependent manner that results in the differential compartmentalization of the various E2F complexes. Consequently, in cycling cells, the majority of the p107-E2F, p130-E2F, and free E2F complexes remain in the cytoplasm. In contrast, almost all of the nuclear E2F activity is generated by pRB-E2F. This complex is present at high levels during G1 but disappears once the cells have passed the restriction point. Surprisingly, dissociation of this complex causes little increase in the levels of nuclear free E2F activity. This observation suggests that the repressive properties of the pRB-E2F complex play a critical role in establishing the temporal regulation of E2F-responsive genes. How the differential subcellular localization of pRB, p107, and p130 contributes to their different biological properties is also discussed.

Animals↗

L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents.

The single most difficult problem in phylogenetic analysis is deciding whether a shared taxonomic character is due to common ancestry or one that appeared independently due to convergence, parallelism, or reversion to an ancestral state. Mammalian L1 retrotransposons undergo periodic amplifications in which multiple copies of the elements are interspersed in the genome. Because these elements apparently are transmitted only by inheritance and are retained in the genome, a shared L1 amplification event can only be an inherited ancestral character. We propose that L1 amplification events can be an excellent tool for analyzing mammalian evolution and demonstrate here how we addressed several refractory problems in rodent systematics using L1 DNA as a taxonomic character.

Animals↗

Distinctive hair changes (pili torti) in Rapp-Hodgkin ectodermal dysplasia syndrome.

An 8-year-old girl with narrow nose, small mouth, maxillary hypoplasia, cleft palate, hypodontia and hypohidrosis is described. Her scalp hair was coarse, dry and wiry. Microscopic examination showed the hair to be twisted at irregular intervals on its long axis, as seen in pili torti. Her mother has the same features; as a child, she had identical hair and is now bald. Both mother and daughter display signs and symptoms of Rapp-Hodgkin's ectodermal dysplasia. The autosomal dominant inheritance of the disease is further supported by the findings in this family.

Adult↗

[Nonbacterial thrombotic endocarditis related to hepatocarcinoma].

A case of a woman with nonbacterial thrombotic endocarditis (NBTE) associated with hepatocarcinoma is here presented. Epidemiologic and clinicopathologic aspects are reviewed, early clinical suspicion may prevent embolization. it represents the first case reported in the national literature.

Aged↗

[Tubercular liver abscess: a case report and discussion of the literature].

A case of an isolated tuberculous abscess of the liver in a 47-years-old woman with a 2-year history of disease is presented. Only 17 similar cases have been reported previously in the literature. The symptomatology of this patient, confused initially with a chronic calculous cholecystitis and then with an hepatic pyogenic abscess exemplify what has been described for this rare disease presentation. A review of the pertinent literature is presented.

Chronic Disease↗

[A solid epithelial papillary-cystic pancreatic tumor. A report of a clinical case and review of the literature].

Solid and papillary epithelial tumor of the pancreas is an uncommon neoplasm of low malignant potential, which occurs mainly in adolescent and young adult females. We report the case of a 17 years old woman, who presented with an abdominal mass, which was diagnosed cytologically by aspiration. The surgical procedure was total excision. Six months post surgery the patient is healthy. As this is a very unusual occurrence, a review of the literature has been made on clinical, histological, radiological and surgical features.

Adolescent↗

[Peutz-Jeghers syndrome. Apropos a familial case at Hospital Arzobispo Loayza].

The Peutz-Jeghers syndrome is a rare dominant autosomic, entity characterized by hyperpigmented lesions on the lips, hands and feet; with presence of gastrointestinal polyps producing acute or chronic anemia, intestinal obstruction, and/or abdominal pain. This polyps histologically are hamartomas; recent studies indicate a real risk for transformations in the malignant neoplasia. The high and low endoscopies and the intraoperative enteroscopy with polypectomy are the election treatment, improving prognosis quality on these patients. We describe a familiar case of a female patient 24 years old showing a repeated picture of intestinal subocclusion; her brother presented a similar clinical picture, and her mother presented the same syndrome, dying of carcinoma in the colon; also her child, at one and a half year old presented hyperpigmented lesions on the lips.

Adult↗