SP1, BUT NOT SP3, FUNCTIONS TO MEDIATE PROMOTER ACTIVATION BY TGF-BETA THROUGH CANONICAL SP1 BINDING-SITES

Citation
Jm. Li et al., SP1, BUT NOT SP3, FUNCTIONS TO MEDIATE PROMOTER ACTIVATION BY TGF-BETA THROUGH CANONICAL SP1 BINDING-SITES, Nucleic acids research, 26(10), 1998, pp. 2449-2456
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
Journal title
ISSN journal
0305-1048
Volume
26
Issue
10
Year of publication
1998
Pages
2449 - 2456
Database
ISI
SICI code
0305-1048(1998)26:10<2449:SBNSFT>2.0.ZU;2-B
Abstract
Transforming growth factor beta (TGF-beta) causes growth arrest at the G1 phase of the cell cycle in most cell types. Both the cyclin depend ent kinase inhibitor p15(INK4B) and p21(Cip1/WAF1) genes have been fou nd to be induced by TGF-beta in human keratinocyte HaCaT cells. Analys es of the human p15 and p21 promoters have led to the identification o f GC-rich sequences capable of binding to Sp1 transcription factors as necessary elements for the TGF-beta induction of both promoters. We r eport here that canonical Sp1 binding sites derived from the SV40 21 b p repeat could also support promoter induction by TGF-beta when placed upstream of a minimal luciferase reporter construct containing only t he TATA and Inr elements. Gel retardation assays identified Sp1, Sp3 a nd Delta Sp3 as major factors binding to the canonical Sp1 sites in Ha CaT cells and that TGF-beta treatment did not change their binding act ivities over a 24 h period. More importantly, GAL4-Sp1, but not GAL4-S p3, chimeric protein supported TGF-beta mediated gene induction from a luciferase reporter construct driven by five GAL4 DNA binding sites, Our results suggest that Sp1 binding site can function as a distinct T GF-beta responsive element for TGF-beta mediated promoter expression a nd Sp1 per se can mediate this response.