| Autor: |
NM Belaid, A Basseville, G Andre-Gregoire, A Fetiveau, L Maillet, F Guillonneau, M Leduc, C Guette, L Desaubry, J. Gavard, F Gautier, PP Juin |
| Rok vydání: |
2022 |
| Předmět: |
|
| DOI: |
10.1101/2022.04.13.488211 |
| Popis: |
In addition to its canonical role as a regulator of mitochondrial outer membrane permeabilization, BCL-xL exerts diverse non canonical functions contributing to cancer cell aggressiveness. In particular it regulates KRAS intracellular activation levels. We herein explored the mechanistic basis for this effect by a spatially restricted biotin-labelling proteomic approach designed to characterize proteins whose proximity to KRAS, used as a bait, is BCL-xL dependant. BCL-xL loss relocalizes KRAS to the vicinity of mitochondrial proteins. Proximal proteins include the mitochondrial scaffold prohibitin 2 (PHB2), which also interacts with BCL-xL and the downregulation of which prevents BCL-xL sensitive effects of KRAS induced contacts between mitochondria and endosomes, and mitochondrial mass decrease. These results argue that BCL-xL prevents a negative feedback regulation of KRAS canonical signaling by KRAS interference with mitochondrial quality control. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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