Cell cycle-dependent switch of up- and down-regulation of human hsp70 geneexpression by interaction between c-Myc and CBF/NF-Y

Citation
T. Taira et al., Cell cycle-dependent switch of up- and down-regulation of human hsp70 geneexpression by interaction between c-Myc and CBF/NF-Y, J BIOL CHEM, 274(34), 1999, pp. 24270-24279
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
274
Issue
34
Year of publication
1999
Pages
24270 - 24279
Database
ISI
SICI code
0021-9258(19990820)274:34<24270:CCSOUA>2.0.ZU;2-3
Abstract
A CCAAT box-binding protein subunit, CBF-C/NF-YC, was cloned as a protein i nvolved in the c-Myc complex formed on the G(1)-specific enhancer in the hu man hsp70 gene. CBF-C/NF-YC directly bound to c-Myc in vitro and in vivo in cultured cells. The CBF/NF-Y.c-Myc complex required the HSP-MYC-B element as well as CCAAT in the hsp70 G(1)-enhancer, while the purified CBF subunit s recognized only CCAAT even in the presence of c-Myc. Both the HSP-MYC-B a nd CCAAT elements were also required for the enhancer activity. In transien t transfection experiments, the CBF/NF-Y.c-Myc complex, as well as transcri ption due to the G(1)-enhancer, was increased by the introduction of c-Myc at low doses but decreased at high doses. The repression of both complex fo rmation and transcription by c-Myc at high doses was abrogated by the intro duction of CBF/NF-Y in a dose-dependent manner. Furthermore, the CBF/NF-Y.c -Myc complex bound to the G(1)-enhancer appeared in the early G(1) phase of the cell cycle when c-Myc was not higly expressed and gradually disappeare d after the c-Myc expression reached its maximum. The results indicate that the cell cycle-dependent expression of the hsp70 gene is regulated by the intracellular amount of c-Myc through the complex formation states between CBF/NF-Y and c-Myc.