Abstract:
:The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop. We have identified the immunophilin, 25kDa FK506-binding protein (FKBP25), previously shown to be regulated by p53-mediated repression, as an MDM2-interacting partner. We show that FKBP25 stimulates auto-ubiquitylation and proteasomal degradation of MDM2, leading to the induction of p53. Depletion of FKBP25 by siRNA leads to increased levels of MDM2 and a corresponding reduction in p53 and p21 levels. These data are consistent with the idea that FKBP25 contributes to regulation of the p53-MDM2 negative feedback loop.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Ochocka AM,Kampanis P,Nicol S,Allende-Vega N,Cox M,Marcar L,Milne D,Fuller-Pace F,Meek Ddoi
10.1016/j.febslet.2009.01.009subject
Has Abstractpub_date
2009-02-18 00:00:00pages
621-6issue
4eissn
0014-5793issn
1873-3468pii
S0014-5793(09)00034-9journal_volume
583pub_type
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