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Titolo:
Endoplasmic reticulum/cytosolic localization of von Hippel-Lindau gene products is mediated by a 64-amino acid region
Autore:
Schoenfeld, AR; Davidowitz, EJ; Burk, RD;
Indirizzi:
Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Microbiol & Immunol, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 Immunol, Bronx, NY 10461 USA Albert Einstein Coll Med, Albert Einstein Comprehens Canc Ctr, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 Canc Ctr, Bronx, NY 10461 USA Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Pediat, Bronx,NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 pt Pediat, Bronx,NY 10461 USA Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Epidemiol & Social Med, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 cial Med, Bronx, NY 10461 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 4, volume: 91, anno: 2001,
pagine: 457 - 467
SICI:
0020-7136(20010215)91:4<457:ERLOVH>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR PROTEIN; BIOLOGICALLY-ACTIVE PRODUCT; RENAL-CELL CARCINOMA; FACTOR MESSENGER-RNA; ELONGIN BC COMPLEX; SOMATIC MUTATIONS; UBIQUITIN LIGASE; VHL GENE; DISEASE; IDENTIFICATION;
Keywords:
endoplasmic reticulum; renal-cell carcinoma; subcellular localization; ubiquitination; von Hippel-Lindau (VHL);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Burk, RD Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Microbiol & Immunol, Ullmann Bldg,Rm 515,1300 Morris Pk Ave, Bronx, NY 10461 USAAlbert Einstein Coll Med Ullmann Bldg,Rm 515,1300 Morris Pk Ave Bronx NY USA 10461
Citazione:
A.R. Schoenfeld et al., "Endoplasmic reticulum/cytosolic localization of von Hippel-Lindau gene products is mediated by a 64-amino acid region", INT J CANC, 91(4), 2001, pp. 457-467

Abstract

Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both the familial cancer syndrome VHL disease and corresponding sporadic tumor types, including renal-cell carcinoma. Subcellular localization of VHL gene products was determined by indirect immunofluorescence. Both native andexogenously expressed VHL proteins displayed a cytoplasmic peri-nuclear immunostaining pattern, which co-localized with markers for the endoplasmic reticulum (ER). In addition, subcellular fractionation indicated that both native and exogenously expressed VHL products are found predominantly in thecytosolic compartment. Deletion analyses demonstrated that a 64-amino acidregion of VHL (residues 114-177) is responsible for cytosolic as well as ER subcellular localization. Taken together, the immunostaining and biochemical fractionation studies suggest that VHL localizes to the cytosolic face of the ER, The relationship between VHL subcellular localization and VHL-associated ubiquitination was examined. Chimeric VHL-green fluorescent protein (GFP) products, which localized to the peri-nuclear region, were shown toundergo ubiquitination. VHL amino acids 114-177 were necessary and sufficient for this modification. Consistent with a role of VHL in ubiquitination,expression of VHL led to enhanced ubiquitination of cellular proteins, andamino acids 114-177 were also critical for this effect. Therefore, amino acids 114-177 were required for accurate VHL subcellular localisation, ubiquitination of VHL-GFP products and VHL-dependent increases in cellular ubiquitination. Since mutations in this region of VHL are frequently detected inrenal-cell carcinomas, these results suggest that proper VHL subcellular localization and associated ubiquitination functions may be necessary for VHL-mediated tumor suppression. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/21 alle ore 07:52:27