Transcriptional regulation of the CDK inhibitor p16(INK4a) gene by a novelpRB-associated repressor, RBAR1

Citation
S. Kaneko et al., Transcriptional regulation of the CDK inhibitor p16(INK4a) gene by a novelpRB-associated repressor, RBAR1, BIOC MOL B, 47(2), 1999, pp. 205-215
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL
ISSN journal
1039-9712 → ACNP
Volume
47
Issue
2
Year of publication
1999
Pages
205 - 215
Database
ISI
SICI code
1039-9712(199902)47:2<205:TROTCI>2.0.ZU;2-H
Abstract
p16, also known as INK4a, CDKN2, or MTS1, plays an important role in the co ntrol of the cell cycle progression, and retinoblastoma protein (pRb) is su ggested to be involved in the transcriptional regulation of p16. However, i t is not fully understood how pRb regulates transcription of the p16 gene. Nuclear proteins prepared only from the pRb-nonfunctional human tumor cells were found to bind to the 5'-flanking sequence of the p16 gene in the pres ence of Zn2+ by electrophoretic mobility shift assay (EMSA). EMSA using mut agenized 5'-flanking sequences as competitors suggested that the sequence a t position -97 to -87 relative to first ATG of the p16 gene was critical fo r protein binding. Transient reporter assay indicated that the sequence ide ntified by EMSA acted as a silencer element in the pRb-nonfunctional tumor cells, showing the presence of a transcriptional repressor associated with functional pRb (RBAR1).