Genomic organization and transcriptional analysis of the human genes coding for caveolin-1 and caveolin-2

被引:23
作者
Fra, AM [1 ]
Pasqualetto, E [1 ]
Mancini, M [1 ]
Sitia, R [1 ]
机构
[1] Ist Sci San Raffaele, DIBIT, I-20132 Milan, Italy
关键词
caveolae; cholesterol homeostasis; sterol responsive element; tumor suppressor;
D O I
10.1016/S0378-1119(99)00559-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Caveolin-1 and caveolin-2 are related proteins involved in the biogenesis of caveolae. The corresponding genes in humans (CAV and CAV2, respectively), have been mapped to a common locus in chromosome 7q31.1, and are possible candidates for the tumor suppressor gene postulated in this region. Here, we show that CAV and CAV2 are independent transcriptional units lying in the same orientation, with CAV2 centromeric and about 17 kb upstream to CAV. The two genes have similar tissue expression patterns. Alternative termination/polyadenylation generates two CAV2 mRNAs. Multiple transcriptional start sites spanning 35 bp upstream from the CAV2 ATG are detected by 5' RACE, consistent with a TATA-less promoter predicted by sequence analysis. The CAV2 promoter region contains two SRE-like boxes resembling those described in the CAV promoter and proposed to link transcription to intracellular cholesterol levels. However, exogenous sterols had only minor effects on CAV and CAV2 RNA levels in HeLa cells, suggesting that SREBPs are not sufficient to regulate caveolin transcription. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:75 / 83
页数:9
相关论文
共 31 条
[1]   The caveolae membrane system [J].
Anderson, RGW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :199-225
[2]   Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol [J].
Bist, A ;
Fielding, PE ;
Fielding, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10693-10698
[3]   Molecular and cellular biology of caveolae - Paradoxes and plasticities [J].
Couet, J ;
Li, SW ;
Okamoto, T ;
Scherer, PE ;
Lisanti, MP .
TRENDS IN CARDIOVASCULAR MEDICINE, 1997, 7 (04) :103-110
[4]   Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1) -: Methylation of a CpG island in the 5′ promoter region of the caveolin-1 gene in human breast cancer cell lines [J].
Engelman, JA ;
Zhang, XL ;
Lisanti, MP .
FEBS LETTERS, 1999, 448 (2-3) :221-230
[5]   Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2, and -3) - Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/731) [J].
Engelman, JA ;
Zhang, XL ;
Galbiati, F ;
Lisanti, MP .
FEBS LETTERS, 1998, 429 (03) :330-336
[6]   Genes encoding human caveolin-1 and -2 are co-localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers [J].
Engelman, JA ;
Zhang, XL ;
Lisanti, MP .
FEBS LETTERS, 1998, 436 (03) :403-410
[7]   Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates anchorage-independent growth [J].
Engelman, JA ;
Wykoff, CC ;
Yasuhara, S ;
Song, KS ;
Okamoto, T ;
Lisanti, MP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (26) :16374-16381
[8]   Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers [J].
Fielding, CJ ;
Bist, A ;
Fielding, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3753-3758
[9]  
Fielding CJ, 1997, J LIPID RES, V38, P1503
[10]   DE-NOVO FORMATION OF CAVEOLAE IN LYMPHOCYTES BY EXPRESSION OF VIP21-CAVEOLIN [J].
FRA, AM ;
WILLIAMSON, E ;
SIMONS, K ;
PARTON, RG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (19) :8655-8659