TGFbeta influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b.
Nat Cell Biol
; 3(4): 400-8, 2001 Apr.
Article
in En
| MEDLINE
| ID: mdl-11283614
ABSTRACT
Transforming growth factor-beta (TGFbeta) is a cytokine that arrests epithelial cell division by switching off the proto-oncogene c-myc and rapidly switching on cyclin-dependent kinase (CDK) inhibitors such as p15INK4b. Gene responses to TGFbeta involve Smad transcription factors that are directly activated by the TGFbeta receptor. Why downregulation of c-myc expression by TGFbeta is required for rapid activation of p15INK4b has remained unknown. Here we provide evidence that TGFbeta signalling prevents recruitment of Myc to the p15INK4b transcriptional initiator by Myc-interacting zinc-finger protein 1 (Miz-1). This relieves repression and enables transcriptional activation by a TGFbeta-induced Smad protein complex that recognizes an upstream p15INK4b promoter region and contacts Miz-1. Thus, two separate TGFbeta-dependent inputs - Smad-mediated transactivation and relief of repression by Myc - keep tight control over p15INK4b activation.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carrier Proteins
/
Trans-Activators
/
Proto-Oncogene Proteins c-myc
/
Transforming Growth Factor beta
/
Zinc Fingers
/
Cyclin-Dependent Kinases
/
Cell Cycle Proteins
/
Cyclin-Dependent Kinase Inhibitor p16
/
Tumor Suppressor Proteins
/
DNA-Binding Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Cell Biol
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos