FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53

Anna Maria Ochocka; Petros Kampanis; Samantha Nicol; Nerea Allende-Vega; Miranda Cox; Lynnette Marcar; Diane Milne; Frances Fuller-Pace; David Meek

doi:10.1016/j.febslet.2009.01.009

FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53

Anna Maria Ochocka, Petros Kampanis, Samantha Nicol, Nerea Allende-Vega, Miranda Cox, Lynnette Marcar, Diane Milne, Frances Fuller-Pace, David Meek

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	621-6
Number of pages	6
Journal	FEBS Letters
Volume	583
Issue number	4
DOIs	https://doi.org/10.1016/j.febslet.2009.01.009
Publication status	Published - 18 Feb 2009

Keywords / Materials (for Non-textual outputs)

Animals
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21
Escherichia coli
Gene Expression Regulation, Neoplastic
Genes, Reporter
Glutathione Transferase
HCT116 Cells
Humans
Luciferases
Mice
Proteasome Endopeptidase Complex
Proto-Oncogene Proteins c-mdm2
RNA, Small Interfering
Recombinant Fusion Proteins
Tacrolimus Binding Proteins
Transfection
Tumor Suppressor Protein p53
Ubiquitin-Protein Ligases
Ubiquitination

Access to Document

10.1016/j.febslet.2009.01.009

Cite this

@article{d29ea09256f54ff88653a1abbc3bb039,

title = "FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53",

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.",

keywords = "Animals, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Escherichia coli, Gene Expression Regulation, Neoplastic, Genes, Reporter, Glutathione Transferase, HCT116 Cells, Humans, Luciferases, Mice, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-mdm2, RNA, Small Interfering, Recombinant Fusion Proteins, Tacrolimus Binding Proteins, Transfection, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination",

author = "Ochocka, {Anna Maria} and Petros Kampanis and Samantha Nicol and Nerea Allende-Vega and Miranda Cox and Lynnette Marcar and Diane Milne and Frances Fuller-Pace and David Meek",

year = "2009",

month = feb,

day = "18",

doi = "10.1016/j.febslet.2009.01.009",

language = "English",

volume = "583",

pages = "621--6",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53

AU - Ochocka, Anna Maria

AU - Kampanis, Petros

AU - Nicol, Samantha

AU - Allende-Vega, Nerea

AU - Cox, Miranda

AU - Marcar, Lynnette

AU - Milne, Diane

AU - Fuller-Pace, Frances

AU - Meek, David

PY - 2009/2/18

Y1 - 2009/2/18

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line, Tumor

KW - Cyclin-Dependent Kinase Inhibitor p21

KW - Escherichia coli

KW - Gene Expression Regulation, Neoplastic

KW - Genes, Reporter

KW - Glutathione Transferase

KW - HCT116 Cells

KW - Humans

KW - Luciferases

KW - Mice

KW - Proteasome Endopeptidase Complex

KW - Proto-Oncogene Proteins c-mdm2

KW - RNA, Small Interfering

KW - Recombinant Fusion Proteins

KW - Tacrolimus Binding Proteins

KW - Transfection

KW - Tumor Suppressor Protein p53

KW - Ubiquitin-Protein Ligases

KW - Ubiquitination

U2 - 10.1016/j.febslet.2009.01.009

DO - 10.1016/j.febslet.2009.01.009

M3 - Article

C2 - 19166840

SN - 0014-5793

VL - 583

SP - 621

EP - 626

JO - FEBS Letters

JF - FEBS Letters

IS - 4

ER -

FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Cite this