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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have cloned cDNA encoding hamster Bcl-2 protein from total RNA of CHO-9 cells by RT-PCR using oligonucleotide primers sharing homology with the sequence of mouse and rat bcl-2. The fragments spanning the total coding region were cloned into pCR4-TOPO and sequenced for verification. The hamster bcl-2 cDNA has a size of 711 nucleotides and encodes a polypeptide of 236 amino acids. Hamster Bcl-2 shares 95.8 and 88.6% similarity with mouse and human Bcl-2, respectively. Northern blot analysis revealed a single 7.5 kb bcl-2 transcript in hamster (CHO-9), mouse (BK4), and rat (H5) cells and a 8.5 kb bcl-2 mRNA in human (HeLa MR) cells. The bcl-2 cDNA (771 bp) was recloned into pcDNA3 and the recombinant construct was transiently transfected into MGMT-deficient HeLa MR cells. Expression of hamster Bcl-2 rendered the cells more resistant to MNNG-induced cytotoxicity, which is consistent with the anti-apoptotic function of Bcl-2.
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PMID:Cloning and functional analysis of cDNA encoding the hamster Bcl-2 protein. 1097 19

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.
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PMID:Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence. 1112 Jun 66

The importance of the Bcl-2 family proteins in normal vertebrate embryogenesis is being recognized; however, their regulatory mechanism is poorly understood. We report here the cloning and characterization of a novel zebrafish Bcl-2 family protein, zfBLP1. The zfBLP1 cDNA is 1942 nucleotides long, encoding a polypeptide of 238 amino acids. The primary sequence of zfBLP1 shares 50% identity to human Bcl-XL, and contains all four conserved BH domains of the Bcl-2 family proteins. Primary sequence analysis identified a consensus ER retention signal at the C-terminal end of zfBLP1. Northern blot analysis indicated that there were two major and two minor zfBLP1 mRNA species expressed during embryonic development. Among the two major mRNA species, the short one, approx. 3 kb in size, was expressed throughout embryonic development, while the long one, approx. 7 kb long, was not detectable until the gastrula stage. These results suggest that zfBLP1 is a novel Bcl-2 family protein under complicated regulations, and is likely to play an important role in zebrafish oogenesis and embryogenesis.
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PMID:Cloning and characterization of zfBLP1, a Bcl-XL homologue from the zebrafish, Danio rerio. 1140 82

It is established that sponges, the phylogenetically oldest still extant phylum of Metazoa, possess key molecules of the apoptotic pathways, that is members from the Bcl-2 family and a pro-apoptotic molecule with death domains. Here we report on transfection studies of human cells with a sponge gene, GCBHP2. Sponge tissue was exposed to heat shock and tributyltin, which caused an upregulation of gene expression of GCBHP2. The cDNA GCBHP2 was introduced into human HEK-293 cells and mouse NIH-3T3 cells; the stable transfection was confirmed by the identification of the transcripts, by Western blotting as well as by immunofluorescence using antibodies raised against the recombinant polypeptide. HEK-293 cells, transfected with GCBHP2, showed high resistance to serum starvation and tributyltin treatment, compared to mock-transfected cells. In contrast to mock-transfected cells, GCBHP2-transfected cells activated caspase-3 to a lower extent. Thus, sponges contain gene(s) involved in apoptotic pathway(s) displaying their function also in human cells.
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PMID:Sponge Bcl-2 homologous protein (BHP2-GC) confers distinct stress resistance to human HEK-293 cells. 1152 44

Apoptosis is meticulously controlled in living organisms. Its dysregulation has been shown to play a key role in a number of human diseases, including neoplastic, cardiovascular, and degenerative disorders. Bcl-2 family member proteins and inhibitors of apoptosis proteins are two major negative regulators of apoptosis. We report here the characterization of novel antiapoptotic protein, fortilin, which we identified through yeast two-hybrid library screening. Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide highly conserved from mammals to plants. Fortilin is structurally unrelated to either Bcl-2 family member proteins or inhibitors of apoptosis proteins. Northern blot analysis showed the fortilin message to be ubiquitous in normal tissue but especially abundant in the liver, kidney, and small intestine. Western blot analysis using anti-fortilin antibody showed more extensive expression in cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from normal tissue (HEK293). Immunocytochemistry using HeLa cells transiently expressing FLAG-tagged fortilin and immunohistochemistry using human breast ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is predominantly localized in the nucleus. Functionally, the transient overexpression of fortilin in HeLa cells prevented them, in a dose-dependent fashion, from undergoing etoposide-induced apoptosis. Consistently, U2OS cells stably expressing fortilin protected the cells from cell death induced by etoposide over various concentrations and durations of exposure. In addition, fortilin overexpression inhibited caspase-3-like activity as assessed by the cleavage of fluorogenic substrate benzyloxycarbonyl-DEVD-7-amido-4-(trifluoromethyl)coumarin. Furthermore, the antisense depletion of fortilin from breast cancer cell line MCF-7 was associated with massive cell death. These data suggest that fortilin represents a novel antiapoptotic protein involved in cell survival and apoptosis regulation.
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PMID:Characterization of fortilin, a novel antiapoptotic protein. 1159 39

Heregulins (HRGs) are a group of polypeptide factors that are encoded by four different HRG genes that can express multiple isoforms through alternate RNA splicing. A number of HRG isoforms possess both growth stimulatory and growth inhibitory functions that are necessary for their important role in the development and maintenance of the heart, nervous system and epithelial cells in multiple organs including the breast. Growth inhibition by HRG relates to its ability to induce apoptosis, differentiation, and cell cycle G(2) arrest. Current studies suggest that HRGs can induce a unique form of apoptosis. In this article, we review recent progress in characterizing and understanding HRG-induced apoptosis. Particular attention has been given to: (1). the activation of caspases-7 and -9; (2). the role of the anti-apoptotic Bcl-2 protein; and (3). the signaling molecules and pathways that regulate HRG-induced apoptosis, including the p38, JNK, mTOR kinase, and PKC alpha kinase.
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PMID:Heregulin-induced apoptosis. 1237 Apr 90

Cortical dysplasia (CD) is a well-recognized cause of intractable epilepsy, especially in children and is characterized histologically by derangements in cortical development and organization. The objective of this study was to expand the current knowledge of altered gene expression in CD as a first step towards in the identification of additional genes operative in the evolution of CD. Surgical specimens were obtained from eight patients (4 males and 4 females; age range 2-38 years; mean 15 years) with a pathologic diagnosis of CD. Nondysplastic temporal neocortex was obtained from a 2-year-old boy with intractable epilepsy and medial temporal lobe ganglioglioma. After total RNA isolation from frozen brain tissues, we carried out gene expression profiling using a cDNA expression array. Differences in gene expressions between CD and the nondysplastic neocortex were confirmed by semi-quantitative conventional reverse transcription-PCR. Three genes (recombination activating gene 1 (RAG1), heat shock 60 kDa protein 1 (HSP-60), and transforming growth factor beta1 (TGF beta1)) were found to be up-regulated more than two-fold in CD, whereas four genes (phosphoinositide-3-kinase regulatory subunit polypeptide 1 [p85 alpha] (PI3K), frizzled homolog 2 [Drosophila], Bcl-2/adenovirus E1B 19 kDa interacting protein (NIP3), and glia maturation factor beta (GMF beta)) were down-regulated to less than 50% of their normal levels. Interestingly, the majority of genes showing altered expression were associated with apoptosis. Our study demonstrates diverse changes in gene expression in CD. However, it remains to be shown which of these are causally related to the evolution of CD.
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PMID:Gene expression profile analyses of cortical dysplasia by cDNA arrays. 1464 2

Fortilin, a potent 172-amino acid antiapoptotic polypeptide (Li, F., Zhang, D., and Fujise, K. (2001) J. Biol. Chem. 276, 47542-47549), binds MCL1, a protein of the antiapoptotic Bcl-2 family. The fortilin-MCL1 interaction stabilizes and increases the half-life of fortilin but not necessarily of MCL1 (Zhang, D., Li, F., Weidner, D., Mnjoyan, Z. H., and Fujise, K. (2002) J. Biol. Chem. 277, 37430-37438). It is not known to what extent each protein depends on the other for its apoptotic activity. Here, we present evidence that fortilin and MCL1 are capable of functioning as antiapoptotic proteins independently of each other. Using a robust small interfering RNA (siRNA)-mediated gene silencing system developed in our laboratory, we analyzed the cytoprotective effects of fortilin and MCL1 together and apart in U2OS cell lines exposed to 5-fluorouracil (5-FU) in both monoclonal and polyclonal cell populations. When MCL1 was silenced by MCL1-targeted siRNA, fortilin was still able to protect cells from 5-FU-induced cytotoxicity in a dose-dependent manner. Conversely, when fortilin was silenced by fortilin-targeted siRNA, MCL1 was also able to protect cells from 5-FU-induced cytotoxicity in a dose-dependent manner. Together, these data clearly suggest that fortilin and MCL1 can exert their cytoprotective activities independently of each other. The silencing of fortilin and MCL1 did not qualitatively change the subcellular localization of MCL1 and fortilin, respectively. The biological significance of fortilin-MCL1 interaction may be that it increases cellular resistance to apoptosis by allowing MCL1, an independently antiapoptotic protein, to stabilize another independently antiapoptotic protein, fortilin.
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PMID:Antiapoptotic protein partners fortilin and MCL1 independently protect cells from 5-fluorouracil-induced cytotoxicity. 1526 75

Among the Bcl-2 family, myeloid cell leukemia-1 (Mcl-1) distinguishes itself from the other pro-survival proteins by its ability to oppose to a wide variety of pro-apoptotic stimuli, short half-life, and presence of polypeptide sequences enriched in proline (P), glutamic acid (E), serine (S) and threonine (T) domains (PEST). Moreover, Mcl-1 undergoes a complex transcriptional, post-transcriptional, and post-translational regulation process. This regulation modifies not only Mcl-1 expression, but also its function. Various extra-cellular stimuli, including cytokines, growth factors, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and IFN, activate pathways which regulate Mcl-1 expression. Furthermore, Mcl-1 can be alternatively spliced into a long (Mcl-1) or a short (Mcl-1S) form. Mcl-1 opposes pro-apoptotic proteins and can be either cleaved or phosphorylated at a post-translational level. Mcl-1-spliced products, Mcl-1-cleaved products, or phosphorylated Mcl-1 have either a pro or an anti-apoptotic function, highlighting the complexity and pivotal role of Mcl-1 regulation. Here we discuss the regulation and function of Mcl-1 in the pathophysiology of multiple myeloma.
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PMID:Mcl-1 regulation and its role in multiple myeloma. 1546 63

Until recently, the lack of molecular probes hampered the determination of the expression of pro-apoptotic and anti-apoptotic genes in sponge. In an approach to solve this problem, the present study describes a variety of cDNAs from the demosponge Suberites domuncula, coding for proteins that are characteristic for the initiation of apoptosis (caspase, MA3, ALG-2 protein), for the prevention of programmed cells death (2 Bcl-2 homology proteins, FAIM-related polypeptide, and DAD-1-related protein), and for morphogenetic processes (retinoid X receptor). They were used as probes to monitor the expression levels in vitro in the allogeneic mixed sponge cell reaction (MSCR) system. In the allogeneic MSCR, two-cell aggregates (primmorphs) from genetically different animals of the same species were positioned next to each other. After approximately 8 days in culture, one of the primmorphs underwent apoptotic death, while the second remained alive. The expression levels of the aforementioned genes were determined by Northern blotting and by in situ hybridization. These experiments revealed that in the apoptotic primmorph, the characteristic apoptotic genes were expressed, while in the non-apoptotic aggregates the cell-survival genes are highly upregulated. Interestingly, the transcript levels of retinoid X receptor were higher in apoptotic primmorphs than in the non-apoptotic aggregate in the assay. Our data show for the first time that in the in vitro MSCR system, allogeneic recognition led to apoptotic cell death in one partner, while the other one survived. We suggest that this process is controlled by a differential expression of the pro-apoptotic and pro-survival genes studied here.
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PMID:Allograft rejection in the mixed cell reaction system of the demosponge Suberites domuncula is controlled by differential expression of apoptotic genes. 1551 43


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