A novel p53-binding domain in CUL7.
CUL7 is a member of the cullin RING ligase family and forms an SCF-like complex with SKP1 and FBXW8. CUL7 is required for normal mouse embryonic development and cellular proliferation, and is highly homologous to PARC, a p53-associated, parkin-like cytoplasmic protein. We determined that CUL7, in a manner similar to PARC, can bind directly to p53 but does not affect p53 expression. We identified a discrete, co-linear domain in CUL7 that is conserved in PARC and HERC2, and is necessary and sufficient for p53-binding. The presence of p53 stabilized expression of this domain and we demonstrate that this p53-binding domain of CUL7 contributes to the cytoplasmic localization of CUL7. The results support the model that p53 plays a role in regulation of CUL7 activity.
Kasper
Jocelyn S
JS
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Arai
Takehiro
T
DeCaprio
James A
JA
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D044842:Cullin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D017385:Sequence Homology; D014166:Transferases; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C506299:CUL7 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D016159:Tumor Suppressor Protein p53; C400192:Cul9 protein, human; D014166:Transferases; D044767:Ubiquitin-Protein Ligases