Independent promoters regulate the expression of two amino terminally distinct forms of latent transforming growth factor-beta binding protein-1 (LTBP-1) in a cell type-specific manner - PubMed (original) (raw)

. 1999 Nov 12;274(46):32619-30.

doi: 10.1074/jbc.274.46.32619.

Affiliations

• PMID: 10551816
• DOI: 10.1074/jbc.274.46.32619

Free article

Independent promoters regulate the expression of two amino terminally distinct forms of latent transforming growth factor-beta binding protein-1 (LTBP-1) in a cell type-specific manner

C Koski et al. J Biol Chem. 1999.

Free article

Abstract

Latent transforming growth factor-beta (TGF-beta)-binding proteins (LTBPs) are components of the extracellular matrix and large latent TGF-beta complexes are secreted by various cells. Human LTBP-1 is known to exist in different forms. LTBP-1L (long) has an amino-terminal extension, which is not found in the smaller LTBP-1S isoform. To study the formation and transcriptional regulation of LTBP-1S and LTBP-1L isoforms, we determined the nucleotide sequences of their 5'-flanking regions. The upstream regions of both isoforms are devoid of TATA boxes but contain other putative binding sites for several transcription factors. Genomic sequencing revealed that LTBP-1L transcript is alternatively spliced to an internal splice acceptor inside exon 1 of LTBP-1S and thus defined the genomic organization of the isoforms. Reporter gene analysis of upstream regions indicated the presence of independent, functional promoters, which regulate the transcription of the isoforms by cell-specific manner. Deletion analyses of the promoter regions revealed specific elements modulating their basal and cell type-specific expression. In SV-40 virus-transformed WI-38 lung fibroblasts a regulatory element repressed the transcription of LTBP-1S by a cell-specific manner. In amniotic epithelial cells, transcription of the LTBP-1S reporter gene construct was down-regulated by a distal upstream element. mRNA levels of the isoforms of LTBP-1 were stimulated in response to TGF-beta1 in WI-38 cells. However, since TGF-beta1 failed to stimulate the transcription of LTBP-1 reporter gene constructs, TGF-beta1 may mediate the induction of the isoforms by post-transcriptional mechanisms. Chromosomal localization of the LTBP-1 gene was refined to 2p22-24.

PubMed Disclaimer

Similar articles

• The murine latent transforming growth factor-beta binding protein (Ltbp-1) is alternatively spliced, and maps to a region syntenic to human chromosome 2p21-22.
  Weiskirchen R, Moser M, Günther K, Weiskirchen S, Gressner AM. Weiskirchen R, et al. Gene. 2003 Apr 10;308:43-52. doi: 10.1016/s0378-1119(03)00464-5. Gene. 2003. PMID: 12711389
• Expression and regulation of latent TGF-beta binding protein-1 transcripts and their splice variants in human glomerular endothelial cells.
  Kwak JH, Woo JS, Shin K, Kim HJ, Jeong HS, Han DC, Kim SI, Park CS. Kwak JH, et al. J Korean Med Sci. 2005 Aug;20(4):628-35. doi: 10.3346/jkms.2005.20.4.628. J Korean Med Sci. 2005. PMID: 16100456 Free PMC article.
• Efficient association of an amino-terminally extended form of human latent transforming growth factor-beta binding protein with the extracellular matrix.
  Olofsson A, Ichijo H, Morén A, ten Dijke P, Miyazono K, Heldin CH. Olofsson A, et al. J Biol Chem. 1995 Dec 29;270(52):31294-7. doi: 10.1074/jbc.270.52.31294. J Biol Chem. 1995. PMID: 8537398
• Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF-beta action.
  Saharinen J, Hyytiäinen M, Taipale J, Keski-Oja J. Saharinen J, et al. Cytokine Growth Factor Rev. 1999 Jun;10(2):99-117. doi: 10.1016/s1359-6101(99)00010-6. Cytokine Growth Factor Rev. 1999. PMID: 10743502 Review.
• Latent TGF-β-binding proteins.
  Robertson IB, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K, Rifkin DB. Robertson IB, et al. Matrix Biol. 2015 Sep;47:44-53. doi: 10.1016/j.matbio.2015.05.005. Epub 2015 May 8. Matrix Biol. 2015. PMID: 25960419 Free PMC article. Review.

Cited by

• Pushing the limits of the scanning mechanism for initiation of translation.
  Kozak M. Kozak M. Gene. 2002 Oct 16;299(1-2):1-34. doi: 10.1016/s0378-1119(02)01056-9. Gene. 2002. PMID: 12459250 Free PMC article. Review.
• Overexpression of latent transforming growth factor-beta 1 (TGF-beta 1) binding protein 1 (LTBP-1) in association with TGF-beta 1 in ovarian carcinoma.
  Higashi T, Sasagawa T, Inoue M, Oka R, Shuangying L, Saijoh K. Higashi T, et al. Jpn J Cancer Res. 2001 May;92(5):506-15. doi: 10.1111/j.1349-7006.2001.tb01123.x. Jpn J Cancer Res. 2001. PMID: 11376559 Free PMC article.
• Abrogation of both short and long forms of latent transforming growth factor-β binding protein-1 causes defective cardiovascular development and is perinatally lethal.
  Horiguchi M, Todorovic V, Hadjiolova K, Weiskirchen R, Rifkin DB. Horiguchi M, et al. Matrix Biol. 2015 Apr;43:61-70. doi: 10.1016/j.matbio.2015.03.006. Epub 2015 Mar 21. Matrix Biol. 2015. PMID: 25805620 Free PMC article.
• LTBPs, more than just an escort service.
  Todorovic V, Rifkin DB. Todorovic V, et al. J Cell Biochem. 2012 Feb;113(2):410-8. doi: 10.1002/jcb.23385. J Cell Biochem. 2012. PMID: 22223425 Free PMC article. Review.
• The latent transforming growth factor beta binding protein (LTBP) family.
  Oklü R, Hesketh R. Oklü R, et al. Biochem J. 2000 Dec 15;352 Pt 3(Pt 3):601-10. Biochem J. 2000. PMID: 11104663 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program