Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep19725
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Funding
- French National Agency for Research (ANR) [ANR-09-BLAN-0292]
- CNRS
- Universite de Strasbourg
- INSERM
- Instruct
- French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01, ANR-10-LABX-0030-INRT]
- French State fund
- European Union Network of Excellence CONTICANET
- Ligue Nationale Contre le Cancer
- Association Sclerose Tubereuse de Bournevilleand
- Odyssea fund
- Canadian Institutes of Health Research [FRN12517]
- MESR, Ecole Doctorale de Cancerologie Paris XI
- Association pour la Recherche sur le Cancer (ARC)
- Institut de Recherche Servier
- Science without Borders (CNPq)
- CAPES-COFECUB
- Federal University of Parana (UFPR, Brazil)
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0292] Funding Source: Agence Nationale de la Recherche (ANR)
- Medical Research Council [MC_U105178788] Funding Source: researchfish
- MRC [MC_U105178788] Funding Source: UKRI
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Translationally Controlled Tumor Protein (TCTP) is anti-apoptotic, key in development and cancer, however without the typical Bcl2 family members' structure. Here we report that TCTP contains a BH3like domain and forms heterocomplexes with Bcl-xL. The crystal structure of a Bcl-xL deletion variantTCTP(11-31) complex reveals that TCTP refolds in a helical conformation upon binding the BH3-groove of Bcl-xL, although lacking the h1-subregion interaction. Experiments using in vitro-vivo reconstituted systems and TCTP+/- mice indicate that TCTP activates the anti-apoptotic function of Bcl-xL, in contrast to all other BH3-proteins. Replacing the non-conserved h1 of TCTP by that of Bax drastically increases the affinity of this hybrid for Bcl-xL, modifying its biological properties. This work reveals a novel class of BH3-proteins potentiating the anti-apoptotic function of Bcl-xL.
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