Loss of H2A.Z Is Not Sufficient to Determine Transcriptional Activity of Snf2-Related CBP Activator Protein or p400 Complexes

The p400 and SRCAP (Snf2-related CBP activator protein) complexes remodel chromatin by catalyzing deposition of histone H2A.Z into nucleosomes. This remodeling activity has been proposed as a basis for regulation of transcription by these complexes. Transcript levels of p21 or Sp1 mRNAs after knockdown of p400 or SRCAP reveals that each regulates transcription of these promoters differently. In this study, we asked whether deposition of H2A.Z within specific nucleosomes by p400 or SRCAP dictates transcriptional activity. Our data indicates that nucleosome density at specific p21 or Sp1 promoter positions is not altered by the loss of either remodeling complex. However, knockdown of SRCAP or p400 reduces deposition of H2A.Z∼50% into all p21 and Sp1 promoter nucleosomes. Thus, H2A.Z deposition is not targeted to specific nucleosomes. These results indicate that the deposition of H2A.Z by the p400 or SRCAP complexes is not sufficient to determine how each regulates transcription. This conclusion is further supported by studies that demonstrate a SRCAPΔATP mutant unable to deposit H2A.Z has similar transcriptional activity as wild-type SRCAP

Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer

Il puntiglio amoroso

IL PUNTIGLIO AMOROSO Il puntiglio amoroso ([1]) Einband ( - ) Titelseite ([1]) Personenindex ([2]) Mutazioni Di Scene ([3]) Atto Primo ([5]) Scena I. ([5]) Scena II. (7) Scena III. (8) Scena IV. (10) Scena V. (11) Scena VI. (12) Scena VII. (14) Scena VIII. (15) Scena XI [i.e. IX]. (16) Scena X. (17) Scena XI. (18) Scena XII. (21) Scena XIII. (22) Scena XIV. (24) Scena XV. (25) Atto Secondo (29) Scena I. (29) Scena II. (30) Scena III. (32) Scena IV. (33) Scena V. (33) Scena VI. (34) Scena VII. (36) Scena VIII. (39) Scena IX. (40) Scena X. (40) Scena XI. (40) Scena XII. (42) Scena XIII. (43) Scena XIV. (43) Scena XV. (44) Scena XVI. (46) Scena XVII. (46) Atto Terzo (52) Scena I. (52) Scena II. (53) Scena III. (54) Scena IV. (55) Scena V. (56) Scena VI. (57) Scena VII. (58) Scena VIII. (58) Scena IX. (62) Scena X. (63) Scena Ultima (63

GTP-Dependent Hydrolysis of Phosphatidylinositol-4,5-bisphosphate by Soluble Phospholipase C from Adult Human Epidermis

The regulation of soluble phosphoinositide-specific phospholipase C from adult human epidermis by guanine nucleotide was investigated. In the presence of physiologic concentrations of Ca++ (1 μM) and Mg++ (1.5 mM), neither phosphatidylinositol (PI) nor phosphatidylinositol-4,5-bis-phosphate (PIP2) were appreciably hydrolyzed. Addition of guanosine-5' -triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-γ-S) significantly stimulated hydrolysis of PIP2, but not PI. Stimulation of PIP2 hydrolysis by GTP was does-dependent between 1–100 μM GTP. Other nucleoside triphosphates and nucleotide analogues were unable to substitute for GTP or GTP-γ-S. A GTP-γ-S-stimulated PIP2 hydrolysis was inhibited by guanosine-5'-O-(2-thiodiphosphate (GDP-β-S). The phospholipase C preparation specifically bound [35S]GTP-γ -S and this binding was also inhibited by GDP-β-S. In addition to a 41,000-dalton pertussis toxin substrate, the phospholipase C preparation contained 3–4 GTP binding proteins with molecular weights between 20,000–30,000. These data demonstrate that human epidermis contains a soluble GTP-dependent phospholipase C activity that specifically hydrolyzes PIP2 and suggest that this reaction is regulated by a GTP-binding protein(s)