التفاصيل البيبلوغرافية
| العنوان: |
Fluctuations in AKT and PTEN Activity Are Linked by the E3 Ubiquitin Ligase cCBL |
| المؤلفون: |
Olazábal Morán, Manuel, Sánchez Ortega, Miriam, Martínez Muñoz, Laura, Hernandez, Carmen, Rodríguez, Manuel S., Mellado, Mario, Carrera, Ana C. |
| المساهمون: |
Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Asociación Española Contra el Cáncer, Gobierno Regional de Madrid BMD-3804, Ministerio de Ciencia e Innovación SAF2016-79195-R, PID2019-106937RB-I00 |
| بيانات النشر: |
MDPI |
| سنة النشر: |
2022 |
| المجموعة: |
idUS - Deposito de Investigación Universidad de Sevilla |
| مصطلحات موضوعية: |
PTEN, CBL, E3 ubiquitin ligase, Phosphatidylinositide 3-kinase, AKT |
| الوصف: |
3-Poly-phosphoinositides (PIP3) regulate cell survival, division, and migration. Both PI3-kinase (phosphoinositide-3-kinase) and PTEN (phosphatase and tensin-homolog in chromosome 10) control PIP3 levels, but the mechanisms connecting PI3-kinase and PTEN are unknown. Using non-transformed cells, the activation kinetics of PTEN and of the PIP3-effector AKT were examined after the addition of growth factors. Both epidermal growth factor and serum induced the early activation of AKT and the simultaneous inactivation of PTEN (at ~5 min). This PIP3/AKT peak was followed by a general reduction in AKT activity coincident with the recovery of PTEN phosphatase activity (at ~10–15 min). Subsequent AKT peaks and troughs followed. The fluctuation in AKT activity was linked to that of PTEN; PTEN reconstitution in PTEN-null cells restored AKT fluctuations, while PTEN depletion in control cells abrogated them. The analysis of PTEN activity fluctuations after the addition of growth factors showed its inactivation at ~5 min to be simultaneous with its transient ubiquitination, which was regulated by the ubiquitin E3 ligase cCBL (casitas B-lineage lymphoma proto-oncogene). Protein-protein interaction analysis revealed cCBL to be brought into the proximity of PTEN in a PI3-kinase-dependent manner. These results reveal a mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL could be new target in strategies designed to modulate PTEN activity in cancer. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
Cells, 10 (11), 2803.; BMD-3804; SAF2016-79195-R; PID2019-106937RB-I00; https://www.mdpi.com/2073-4409/10/11/2803/htm; https://idus.us.es/handle//11441/139182 |
| الاتاحة: |
https://idus.us.es/handle//11441/139182 |
| Rights: |
Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.A6FE5127 |
| قاعدة البيانات: |
BASE |