Isolation of Markers for Chondro-osteogenic Differentiation Using cDNA Library Subtraction

Deleersnijder, Willy; Hong, Guizhu; Cortvrindt, Rita R.; Poirier, Christophe; Tylzanowski, Przemko; Pittois, Karen; Marck, Eric Van; Merregaert, J.

doi:10.1074/jbc.271.32.19475

Cited by 96 publications

(50 citation statements)

References 49 publications

(32 reference statements)

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“…BRI1 is also a type II transmembrane protein of 264 amino acids, which is primarily expressed in chondrocytes (31). FLAG-BRI1 shares overall topology with FLAG-BRI3 as depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

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BRI3 Inhibits Amyloid Precursor Protein Processing in a Mechanistically Distinct Manner from Its Homologue Dementia Gene BRI2

Matsuda

D’Adamio

2009

Journal of Biological Chemistry

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Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of ␤ amyloid (A␤) peptides. A␤ is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing: ␤-secretase, followed by ␥-secretase. Here, we show that BRI3, a member of the BRI gene family that includes the familial British and Danish dementia gene BRI2, interacts with APP and serves as an endogenous negative regulator of A␤ production. BRI3 colocalizes with APP along neuritis in differentiated N2a cells; endogenous BRI3-APP complexes are readily detectable in mouse brain extract; reducing endogenous BRI3 levels by RNA interference results in increased A␤ secretion. BRI3 resembles BRI2, because BRI3 overexpression reduces both ␣-and ␤-APP cleavage. We propose that BRI3 inhibits the various processing of APP by blocking the access of ␣-and ␤-secretases to APP. However, unlike BRI2, the binding of BRI3 to the ␤-secretase cleaved APP C-terminal fragment is negligible and BRI3 does not cause the massive accumulation of this APP fragment, suggesting that, unlike BRI2, BRI3 is a poor ␥-cleavage inhibitor. Competitive inhibition of APP processing by BRI3 may provide a new approach to AD therapy and prevention.About 1% of humans aged 60 -64 years have AD, 2 increasing steadily to as many as 35-40% after age 85 (1). AD progressively leads to a severely impaired state and complete social dependence. At autopsy, cerebral atrophy, neurofibrillary tangles, and amyloid plaques are observed in the hippocampus, entorhinal cortex, amygdala, and other areas. Tangles consist of intraneuronal masses of helically wound filaments of the hyperphosphorylated protein, Tau. Plaques are extracellular deposits of A␤, a peptide derived from cleavage of APP, surrounded by dystrophic neurites. Most AD cases present A␤ deposits in cortical and/or meningeal microvessels. In a minority of cases, this vascular cerebral amyloid angiopathy is rather severe (2).APP is a type I transmembrane protein that undergoes a series of proteolytic cleavages (3). ␤-Secretase cleaves APP into a soluble ectodomain (sAPP␤) and a membrane-bound C-terminal fragment of 99 amino acids (C99). C99 is cleaved by the ␥-secretase, which consists of a multicomponent complex composed of presenilins (PS1 and PS2), Nicastrin, PEN2, and APH1 (4). The ␥-cleavage releases two peptides: A␤ peptide, consisting of 2 major species of 40 and 42 amino acids (A␤40 and A␤42, respectively) and an intracellular product APP intracellular domain (AID)/AICD. Several findings point to the short AID/AICD as a biologically active intracellular peptide, which may modulate cell death, Notch signaling, gene transcription, and Ca 2ϩ homeostasis (5-19). In an alternative pathway, APP is processed by ␣-secretase within the A␤ sequence, leading to the production of the soluble sAPP␣ ectodomain and a membrane-bound C-terminal fragment of 83 amino acids (C83). For aged patients, a family history of dementia is a major risk factor for AD, and 10 -15% of all AD subjects have a family history c...

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“…BRI1 is also a type II transmembrane protein of 264 amino acids, which is primarily expressed in chondrocytes (31). FLAG-BRI1 shares overall topology with FLAG-BRI3 as depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One of the clones isolated contained the entire BRI3 cDNA. BRI3 was originally cloned as a type II transmembrane protein of 267 amino acids (30,31). Similar to BRI2, BRI3 is also cleaved by furin or furinlike convertases, and the C-terminal peptide is secreted (32).…”

Section: Resultsmentioning

confidence: 99%

BRI3 Inhibits Amyloid Precursor Protein Processing in a Mechanistically Distinct Manner from Its Homologue Dementia Gene BRI2

Matsuda

D’Adamio

2009

Journal of Biological Chemistry

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“…Identi®cation and isolation of di erentially expressed transcripts is generally achieved by one of the following methods: di erential display (DD) and related techniques (Liang and Pardee, 1992); representational di erence analysis (RDA) (Lisitsyn et al, 1993); enzymatic degradation subtraction (Zeng et al, 1994); techniques involving physical removal of common sequences (Akopian and Wood, 1995;Deleersnijder et al, 1996); suppression subtractive hybridization; di erential screening or Figure 4 Di erential screening cDNA clones from SSH. After PCR ampli®cation and denaturation, the cDNA fragment of each clone obtained by SSH was arrayed in duplicate on each blot.…”

Section: Discussionmentioning

confidence: 99%

Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor

Zhang

DuBois

2001

Oncogene

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Numerous reports suggest that use of nonsteroidal anti-in¯ammatory drugs (NSAIDs) decrease mortality from colorectal cancer. To better understand all of the mechanisms underlying this e ect, the global pattern of gene expression in colon carcinoma cells following treatment with NS-398, a selective cyclooxygenase-2 inhibitor was evaluated. We utilized suppression subtractive hybridization combined with di erential screening to identify genes whose expression was a ected following treatment. Among the subtracted cDNA fragments con®rmed as di erentially expressed, there were two which are known to be involved in the regulation of cell adhesion (human FAT and proto-cadherin-7). We identi®ed two other genes whose levels were decreased and these are known to be involved in the regulation of cell proliferation (cyclin K and p-100). We identi®ed additional genes which are involved in di erent signaling pathways which regulate programmed cell death (Dynamin 2, Pdcd4 and LIP.1). These results provide evidence that some of the e ects of NS-398 on carcinoma cells may be due to modulation of genes which regulate programmed cell death, cell proliferation and cell ± cell communication. Additional studies are underway to determine the biological function of the novel genes that were identi®ed. Oncogene (2001) 20, 4450 ± 4456.

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“…BRI2 belongs to an evolutionary conserved multigene family comprising at least three homologues in both mouse and humans all bearing the same genomic organization (14,16,17). BRI2 is broadly expressed in peripheral organs as well as in the brain, in which it is ubiquitously present in white and gray matter but shows more abundant distribution in hippocampus and cerebellum compared with cerebral cortex (12).…”

Section: A␤mentioning

confidence: 99%

BRI2 Interacts with Amyloid Precursor Protein (APP) and Regulates Amyloid β (Aβ) Production

Fotinopoulou

Tsachaki

Vlavaki

et al. 2005

Journal of Biological Chemistry

104

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Transmembrane proteins BRI2 and amyloid precursor protein (APP) co-localize with amyloid ␤ (A␤) lesions in sporadic Alzheimer disease and mutations in both precursor proteins are linked to early-onset familial cases of cerebral amyloidosis associated with dementia and/or cerebral hemorrhage. A specific interaction between BRI2 and APP was unveiled by immunoprecipitation experiments using transfected and non-transfected cells. The use of deletion mutants further revealed that stretches 648 -719 of APP751 and 46 -106 of BRI2, both inclusive of the full transmembrane domains, are sufficient for the interaction. Removal of most of the APP and BRI2 extracellular domains without affecting the interaction implies that both proteins interact when are expressed on the same cell membrane (cis) rather than on adjacent cells (trans). The presence of BRI2 had a modulatory effect on APP processing, specifically increasing the levels of cellular APP as well as ␤-secretasegenerated COOH-terminal fragments while decreasing the levels of ␣-secretase-generated COOH-terminal fragments as well as the secretion of total APP and A␤ peptides. Determining the precise molecular pathways affected by the specific binding between APP and BRI2 could result in the identification of common therapeutic targets for these sporadic and familial neurodegenerative disorders. A␤,1 a 39 -42-amino acid peptide of unknown biological function normally present in biological fluids, is also the main constituent of parenchymal and vascular amyloid deposits characteristic of Alzheimer disease (AD) (reviewed in Ref. 1). It is an internal fragment of the larger type-I transmembrane amyloid precursor protein APP (also referred as A␤PP), which exists in several isoforms of different length, ranging from 695 to 770 residues (2, 3). From all these APP isoforms, A␤ is normally generated by proteolytic processing through the sequential action of ␤-and ␥-secretases. Within amyloid lesions, a number of unrelated components collectively known as amyloid-associated proteins (amyloid P-component, ␣1-antichymotrypsin, apoE, apoJ, complement components, vitronectin, extracellular matrix proteins, and APP, among others) co-localize with fibrillar and non-fibrillar A␤, as shown by immunohistochemical studies (4 -10). It is not clear whether these proteins are important for the mechanism of amyloidogenesis or just innocent bystanders. Recently, it was reported that a novel protein BRI2 was abundant in dystrophic neurites, in senile plaques, and around vessels in ischemic lesions in AD and was also detected in Lewy neurites in cases of dementia with Lewy bodies and Parkinson disease (11). Of interest, mutations at or near the stop codon of BRI2 are associated with dementia and cerebellar ataxia in kindreds of British (12) and Danish (13) origin.BRI2 is a type-II transmembrane protein encoded by the single gene BRI2 (also known as ITM2B and E25B) located on the long arm of chromosome 13 (12, 14 -16). BRI2 belongs to an evolutionary conserved multigene family comprising at least...

show abstract

Isolation of Markers for Chondro-osteogenic Differentiation Using cDNA Library Subtraction

Cited by 96 publications

References 49 publications

BRI3 Inhibits Amyloid Precursor Protein Processing in a Mechanistically Distinct Manner from Its Homologue Dementia Gene BRI2

BRI3 Inhibits Amyloid Precursor Protein Processing in a Mechanistically Distinct Manner from Its Homologue Dementia Gene BRI2

Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor

BRI2 Interacts with Amyloid Precursor Protein (APP) and Regulates Amyloid β (Aβ) Production

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