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Title: Reciprocal repression between P53 and TCTP
Authors: Amson, Robert *
Pece, Salvatore *
Lespagnol, Alexandra
Vyad, Rajesh
Mazzarol, Giovanni
Tosoni, Daniela
Colaluca, Ivan
Viale, Giuseppe
Ferreira, Sylvie Rodrigues
Wynendaele, Jessika
Chaloin, Olivier
hoebeke, Johan
Marine, Chris
Di Fiore, Pier Paolo
Telerman, Adam # ×
Issue Date: 11-Dec-2011
Publisher: Nature Pub. Co.
Series Title: Nature Medicine vol:18 issue:1 pages:91-99
Abstract: Screening for genes that reprogram cancer cells for the tumor reversion switch identified TCTP (encoding translationally controlled tumor protein) as a crucial regulator of apoptosis. Here we report a negative feedback loop between P53 and TCTP. TCTP promotes P53 degradation by competing with NUMB for binding to P53-MDM2–containing complexes. TCTP inhibits MDM2 auto-ubiquitination and promotes MDM2-mediated ubiquitination and degradation of P53. Notably, Tctp haploinsufficient mice are sensitized to P53-dependent apoptosis. In addition, P53 directly represses TCTP transcription. In 508 breast cancers, high-TCTP status associates with poorly differentiated, aggressive G3-grade tumors, predicting poor prognosis (P < 0.0005). Tctp knockdown in primary mammary tumor cells from ErbB2 transgenic mice results in increased P53 expression and a decreased number of stem-like cancer cells. The pharmacological compounds sertraline and thioridazine increase the amount of P53 by neutralizing TCTP's action on the MDM2-P53 axis. This study links TCTP and P53 in a previously unidentified regulatory circuitry that may underlie the relevance of TCTP in cancer.
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Molecular Cancer Biology
* (joint) first author
× corresponding author
# (joint) last author

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