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Titolo:
THE MICROPHTHALMIA GENE-PRODUCT INTERACTS WITH THE RETINOBLASTOMA PROTEIN IN-VITRO AND IS A TARGET FOR DEREGULATION OF MELANOCYTE-SPECIFIC TRANSCRIPTION
Autore:
YAVUZER U; KEENAN E; LOWINGS P; VACHTENHEIM J; CURRIE G; GODING CR;
Indirizzi:
MARIE CURIE RES INST,EUKARYOT TRANSCRIPT LAB OXTED RH8 0TL SURREY ENGLAND MARIE CURIE RES INST,EUKARYOT TRANSCRIPT LAB OXTED RH8 0TL SURREY ENGLAND
Titolo Testata:
Oncogene
fascicolo: 1, volume: 10, anno: 1995,
pagine: 123 - 134
SICI:
0950-9232(1995)10:1<123:TMGIWT>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOVIRUS E1A PROTEINS; TYROSINASE-RELATED PROTEIN; OCTAMER-BINDING-PROTEIN; HEAVY-CHAIN ENHANCER; DNA-SYNTHESIS; REGULATORY FUNCTIONS; INDIVIDUAL PRODUCTS; MALIGNANT-MELANOMA; EPITHELIAL-CELLS; CELLULAR PROTEIN;
Keywords:
MICROPHTHALMIA RETINOBLASTOMA; MELANOCYTE-SPECIFIC TRANSCRIPTION; E1A; TRANSCRIPTION REPRESSION; BASIC HELIX-LOOP-HELIX FACTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
86
Recensione:
Indirizzi per estratti:
Citazione:
U. Yavuzer et al., "THE MICROPHTHALMIA GENE-PRODUCT INTERACTS WITH THE RETINOBLASTOMA PROTEIN IN-VITRO AND IS A TARGET FOR DEREGULATION OF MELANOCYTE-SPECIFIC TRANSCRIPTION", Oncogene, 10(1), 1995, pp. 123-134

Abstract

Little is known of the molecular mechanisms underlying the differentiation of the melanocyte from the melanoblast or the progression from the melanocyte to a malignant melanoma. Since the adenovirus E1A products have proved a useful tool for understanding control of differentiation in other systems, we explored the possibility of using E1A as a probe for factors controlling melanocyte-specific gene expression and differentiation. The results obtained show that the adenovirus E1A 13S, but not the 12S, product can transform the highly pigmented and TPA-dependent melanocyte cell line melan-a, Transformation is characterised by a morphological change, loss of TPA-dependence, the ability to growin soft agar and strikingly, loss of pigmentation which correlates with loss of expression of the melanocyte-specific TRP-1 and tyrosinase genes, Cotransfection assays demonstrated that repression of TRP-1 by E1A correlated with E1A binding to p105Rb and p300, with the target inthe TRP-1 promoter being the M-box, an 11 bp basic-Helix-loop-Helix (bHLH) factor-binding motif conserved between melanocyte-specific promoters, Consistent with the M-box acting as a target for E1a-mediated transcription repression, we also show that the basic-helix-loop-helix-leucine zipper (bHLH-LZ) protein (Mi) encoded by the microphthalmia gene (mi), which is required for pigment cell differentiation, is a positive acting transcription factor which can interact with the retinoblastoma product in vitro and activate the TRP-1 promoter, Moreover, expression of the mi gene was reduced around 50-fold in the non-pigmented E1a-transformed melan-a cells compared to the nontransformed melan-a cell line, with ectopic expression of Mi able to prevent repression of the tyrosinase and TRP-1 promoters in the presence of E1A, Mi thereforeappears to play a crucial role in melanocyte-specific gene expression. The parallels between repression of myogenesis and muscle cell bHLH factors, and Mi and melanocyte differentiation are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 14:31:42