p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate

BACKGROUND: p51 (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti-cancer therapy. METHODS: In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti-oncogenesis in vitro and in vivo. RESULTS: Overexpression of p51A revealed an anti-proliferative effect in vitro in all the cancer cells examined in this study. The anchorage-dependent and -independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53-inducible genes, indicating that the mechanisms controlling p51- and p53-mediated tumor suppression differed. CONCLUSIONS: Our observations indicate that, although p51 exhibited reduced anti-oncogenetic effects compared with p53, it cooperatively enhanced the anti-tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy.     

Ectodermal factor restricts mesoderm differentiation by inhibiting p53

During gastrulation of the amphibian embryo, specification of the three germ layers, endo-, ecto-, and mesoderm, is regulated by maternal and zygotic mechanisms. Although it is known that mesoderm specification requires the cooperation between TGF-beta signaling and p53 activity and requires maternal factors, essential zygotic factors have been elusive. Here, we report that the Zn-finger protein XFDL156 is an ectodermal, zygotic factor that suppresses mesodermal differentiation. XFDL156 overexpression suppresses mesodermal markers, and its depletion induces aberrant mesodermal differentiation in the presumptive ectoderm. Furthermore, we find that XFDL156 and its mammalian homologs interact with the C-terminal regulatory region of p53, thereby inhibiting p53 target gene induction and mesodermal differentiation. Thus, XFDL156 actively restricts mesodermal differentiation in the presumptive ectoderm by controlling the spatiotemporal responsiveness to p53.     

Abstract heterarchy: time/state-scale re-entrant form

A heterarchy is a dynamical hierarchical system inheriting logical inconsistencies between levels. Because of these inconsistencies, it is very difficult to formalize a heterarchy as a dynamical system. Here, the essence of a heterarchy is proposed as a pair of the property of self-reference and the property of a frame problem interacting with each other. The coupling of them embodies a one-ity inheriting logical inconsistency. The property of self-reference and a frame problem are defined in terms of logical operations, and are replaced by two kinds of dynamical system, temporal dynamics and state-scale dynamics derived from the same "liar statement". A modified tent map serving as the temporal dynamics is twisted and coupled with a tent map serving as the state-scale dynamics, and this results in a discontinuous self-similar map as a dynamical system. This reveals that the state-scale and temporal dynamics attribute to the system, and shows both robust and emergent behaviors.     

Ecological Aspects of the Downstream Migration of Introduced European Eels in the Uono River, Japan

We examined the species composition, timing of downstream migration, and biological characteristics of eels using catches at three commercial weirs from 1996 to 1998 in the Uono River, Niigata Prefecture, Japan, which is located farther north in the Japan Sea than where most Japanese eels, Anguilla japonica, recruit. Analyses of a sub-sample of the 292 eels caught in the weirs found that 93.6% were introduced European eels, Anguilla anguilla, that were sexually maturing silver phase eels. Their average age based on otolith annuli was 10.2 years, indicating a relatively high average growth rate of 6.3 cm year^–1. Catch records in 1996 and 1997 indicated that downstream migration occurred sporadically from the middle of August to the end of November and that catches generally coincided with abrupt increases in water discharge and drops in water temperature. The highest catches in both years occurred between the last quarter and new moon. These findings were similar to studies on this species in Europe and indicate that A. anguilla can grow rapidly, begin maturation, and start downstream migration far from its native range. This discovery of introduced eels initiating their spawning migration at the same time as A. japonica raises concerns about the potential impact of interbreeding between species and the possible effects on the fishery resources of A. japonica.     

Immunohistochemical evidence for the existence of rat cytosolic sialidase in rat skeletal muscles

 Histochemical evidence is required to demonstrate the presence of biochemically defined cytosolic sialidase. To meet this requirement, we examined the immunohistochemical localization of the enzyme in rat skeletal muscles. Sections of chemically fixed tissues were incubated with a polyclonal antibody raised against a synthetic peptide which corresponded to a part of the enzyme protein. After incubation with the primary antibody, cryosections for fluorescence microscopy and resin sections for electron microscopy were incubated with a fluorochrome- and colloidal gold-labeled secondary antibody, respectively. Immunofluorescence was diffusely distributed in the muscle fibers and was also found in the perimysium and blood vessels. Many immunogold particles were scattered over the sarcoplasm, myofibrils, nucleoplasm, and matrix of mitochondria. The immunogold particles were also found in the equivalent compartments of axons, Schwann cells, and cells of endomysium and blood vessels. The specificity of the primary antibody was elucidated by immunoblotting and an immunoprecipitation test. These findings clearly indicate that this type of sialidase is essentially located in the cytosolic compartment. Consequently, the name, cytosolic sialidase, will be appropriate for this enzyme. Additionally it is indicated that this enzyme is also present in cells other than skeletal muscle fibers. Accepted: 29 January 1997     

Histone H3 peptides incorporating modified lysine residues as lysine-specific demethylase 1 inhibitors

Lysine-specific demethylase 1 (LSD1) is a flavin-dependent enzyme that removes methyl groups from mono- or dimethylated lysine residues at the fourth position of histone H3. We have previously reported several histone H3 peptides containing an LSD1 inactivator motif at Lys-4. In this study, histone H3 peptides having a trans-2-phenylcyclopropylamine (PCPA), a 2,5-dihydro-1H-pyrrole, and a 1,2,3,6-tetrahydropyridine moiety at Lys-4 were prepared along with related compounds possessing a shorter side chain at the fourth position. Enzymatic assays showed that PCPA peptides containing a longer side chain, which can react with FAD in the active site, are potent LSD1-selective inhibitors.