Michael P Cuddy

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With the euchromatic portion of several mammalian genomes now sequenced, emphasis has turned to ascertaining the functions of gene products. A method for targeting destruction of selected proteins in mammalian cells is described, based on the ubiquitin-independent mechanism by which ornithine decarboxylase (ODC) is degraded by the 26S proteasome in(More)
The bcl2 protooncogene was originally discovered because of its involvement in t(14;18) chromosomal translocations frequently found in non-Hodgkin's lymphomas. The expression of this gene is reported to be highly tissue specific, with bcl2 mRNAs being readily detectable only in hematolymphoid tissues and brain. To explore the possible involvement of bcl2 in(More)
A gene-transfer approach was used to explore the function of the BCL2 (B-cell lymphoma/leukemia 2) gene in a human T-cell line, Jurkat. Though stable introduction of a BCL2 expression plasmid into Jurkat T cells was by itself insufficient, the combined transfer of BCL2 and MYC genes markedly enhanced the tumorigenicity of these cells in athymic mice.(More)
Endoplasmic reticulum (ER) stress occurs when unfolded proteins accumulate in the lumen of the organelle, triggering signal transduction events that contribute either to cellular adaptation and recovery or alternatively to cellular dysfunction and death. ER stress has been implicated in numerous diseases. To identify novel modulators of ER stress, we(More)
The unfolded protein response (UPR) or endoplasmic reticulum (ER) stress response is a physiological process enabling cells to cope with altered protein synthesis demands. However, under conditions of obesity, prolonged activation of the UPR has been shown to have deteriorating effects on different metabolic pathways. Here we identify Bax inhibitor-1(More)
Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes cells to apoptosis, and functions as a transcriptional repressor. We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-kappaB, including cIAP2, in human tumor cell lines. Daxx interacts with RelB and inhibits RelB-mediated(More)
The BCL2 (B cell lymphoma/leukemia-2) and C-HA-RAS oncogenes encode membrane-associated proteins of 26 and 21 kilodaltons, respectively. Although RAS proteins have long been known for their ability to bind and hydrolyze GTP, recent investigations suggest that BCL2 encodes a novel GTP-binding protein (S. Haldar, C. Beatty, Y. Tsujimoto, and C. M. Croce,(More)
Nuclear receptor TR3/Nur77/NR4A1 binds several antiapoptotic Bcl-2-family proteins (Bcl-B, Bcl-2, Bfl-1) in a non-BH3-dependent manner. A 9-amino-acid peptide derived from full-length TR3 with polyarginine tail (TR3-r8) recapitulates TR3's binding specificity, displaying high affinity for Bcl-B. TR3-r8 peptide was used to screen for small molecule Bcl-B(More)
BACKGROUND The protein encoded by the bcl-2 (B cell lymphoma/leukemia-2) proto-oncogene has been implicated in the regulation of lymphocyte cell survival and has been shown to interfere with programmed cell death (apoptosis). Recently, controversy has emerged regarding the expression of bcl-2 in circulating peripheral blood lymphocytes (PBL) and its(More)
Previous reports have demonstrated that the phospholemman (PLM), a 72-residue plasma-membrane protein enriched in skeletal muscle and heart, is a major substrate phosphorylated in response to insulin and adrenergic stimulation. Here we describe the isolation and characterization of human and rat PLM cDNA from the heart. Both PLM proteins share significant(More)