Involvement of the DNA Repair Protein hHR23 in p53 Degradation
AUTOR(ES)
Glockzin, Sandra
FONTE
American Society for Microbiology
RESUMO
The stability of the tumor suppressor protein p53 is regulated via the ubiquitin-proteasome-dependent proteolytic pathway. Like most substrates of this pathway, p53 is modified by the attachment of polyubiquitin chains prior to proteasome-mediated degradation. However, the mechanism(s) involved in the delivery of polyubiquitylated p53 molecules to the proteasome are currently unclear. Here, we show that the human DNA repair protein hHR23 binds to polyubiquitylated p53 via its carboxyl-terminal ubiquitin-associated (Uba) domain shielding p53 from deubiquitylation in vitro and in vivo. In addition, downregulation of hHR23 expression within cells by RNA interference results in accumulation of p53. Since the Ubl domain of hHR23 has been shown to interact with the 26S proteasome, we propose that hHR23 is intrinsically involved in the delivery of polyubiquitylated p53 molecules to the proteasome. In this model, the Uba domain of hHR23 binds to polyubiquitin chains formed on p53 and protects them from deubiquitylation, while the Ubl domain delivers the polyubiquitylated p53 molecules to the proteasome.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=309646Documentos Relacionados
- DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a
- Identification and characterization of XPC-binding domain of hHR23B.
- p53CP, a putative p53 competing protein that specifically binds to the consensus p53 DNA binding sites: A third member of the p53 family?
- ATM-Mediated Stabilization of hMutL DNA Mismatch Repair Proteins Augments p53 Activation during DNA Damage
- Mutation of Mouse p53 Ser23 and the Response to DNA Damage