The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain.
J Biol Chem
; 278(45): 44255-64, 2003 Nov 07.
Article
in En
| MEDLINE
| ID: mdl-12947099
ABSTRACT
The cell cycle-regulated B-Myb transcription factor is required for early embryonic development and is implicated in regulating cell growth and differentiation. In addition to its transcriptional regulatory properties, recent data indicate that B-Myb can release active cyclin/Cdk2 activity from the retinoblastoma-related p107 protein by directly interacting with the p107 N terminus. As this p107 domain has homology to the cyclin-binding domains of the p21(Waf1/Cip1) family of cyclin-dependent kinase inhibitors (CKIs), we investigated in this study whether B-Myb could also interact with these CKIs. No in vivo interaction was found with either p21(Waf1/Cip1) or p27(KIP1), however, binding to p57(KIP2) was readily detectable in both in vivo and in vitro assays. The B-Myb-interacting region of p57(KIP2) mapped to the cyclin-binding domain. Consistent with this, B-Myb competed with cyclin A2 for binding to p57(KIP2), resulting in release of active cyclin/Cdk2 kinase. Moreover, B-Myb partially overcame the ability of p57(KIP2) to induce G1 arrest in Saos-2 cells. Despite similarities with previous p107 studies, the B-Myb domains required for interaction with p57(KIP2) were quite different from those implicated for p107. Thus, it is evident that B-Myb may promote cell proliferation by a non-transcriptional mechanism that involves release of active cyclin/Cdk2 from p57(KIP2) as well as p107.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Proteins
/
Trans-Activators
/
Cyclins
/
Cyclin-Dependent Kinases
/
Cell Cycle Proteins
/
DNA-Binding Proteins
Language:
En
Journal:
J Biol Chem
Year:
2003
Document type:
Article
Affiliation country:
United kingdom