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The deficits characteristic of Alzheimer's disease (AD) are believed to result, at least in part, from the neurotoxic effects of beta-amyloid peptides, a set of 39-43 amino acid fragments derived proteolytically from beta-amyloid precursor protein (APP). APP also is cleaved intracytoplasmically at Asp-664 to generate a second cytotoxic peptide, APP-C31, but(More)
In addition to its documented role in the pro-teolytic processing of Notch-1 and the ␤-amyloid precursor protein, presenilin 1 (PS1) associates with ␤-cate-nin. In this study, we show that this interaction plays a critical role in regulating ␤-catenin/T Cell Factor/Lym-phoid Enhancer Factor-1 (LEF) signaling. PS1 deficiency results in accumulation of(More)
Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane(More)
The transcriptional repressor PLZF was identified by its translocation with retinoic acid receptor alpha in t(11;17) acute promyelocytic leukemia (APL). Ectopic expression of PLZF leads to cell cycle arrest and growth suppression, while disruption of normal PLZF function is implicated in the development of APL. To clarify the function of PLZF in cell growth(More)
In addition to its well-established role in gamma-secretase cleavage, presenilin (PS) also plays a role in regulating the stability of cytosolic beta-catenin, a protein involved in Wnt signaling. Several familial Alzheimer's disease-associated PS1 mutations have been shown to increase the stability of the signaling pool of beta-catenin, correlating with(More)
In addition to its documented role in the pro-teolytic processing of Notch-1 and the ␤-amyloid precursor protein, presenilin 1 (PS1) associates with ␤-cate-nin. In this study, we show that this interaction plays a critical role in regulating ␤-catenin/T Cell Factor/Lym-phoid Enhancer Factor-1 (LEF) signaling. PS1 deficiency results in accumulation of(More)
The multiplicity of transcription factors involved in hematologic malignancies suggests a complicated scenario in which many different molecular mechanisms lead to malignant transformation. We hypothesized that some of these proteins might physically and functionally interact and thus mechanistically link different diseases. The ETO protein of t(8;21) acute(More)
B-cell antigen receptor (BCR)-mediated signaling plays a critical role in chronic lymphocytic leukemia (CLL) pathogenesis and gives an in vitro survival advantage to B cells isolated from patients with unfavorable prognostic factors. In this study, we undertook to elucidate the signaling intermediates responsible for this biologic alteration. In responding(More)
lymphoma oncoprotein The ETO protein of t(8;21) AML is a corepressor for the Bcl-6 B-cell (795 articles) Oncogenes and Tumor Suppressors (4217 articles) Neoplasia (746 articles) Apoptosis Articles on similar topics can be found in the following Blood collections Information about subscriptions and ASH membership may be found online at: digital object(More)
B-cell antigen receptor (BCR)–mediated signaling plays a critical role in chronic lymphocytic leukemia (CLL) pathogene-sis and gives an in vitro survival advantage to B cells isolated from patients with unfavorable prognostic factors. In this study, we undertook to elucidate the sig-naling intermediates responsible for this biologic alteration. In(More)
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