Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog

Autor: Ralph Rodriguez, Laurent Ruel, Armel Gallet, Laurence Lavenant-Staccini, Pascal P. Thérond
Přispěvatelé: Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
Rok vydání: 2003
Předmět:
MESH: Signal Transduction
Kinesins
MESH: Receptors
G-Protein-Coupled

Receptors
G-Protein-Coupled

Transduction (genetics)
0302 clinical medicine
MESH: Gene Expression Regulation
Developmental

[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Drosophila Proteins
MESH: Animals
Integral membrane protein
0303 health sciences
Kinase
Gene Expression Regulation
Developmental

MESH: Transcription Factors
Smoothened Receptor
Cell biology
DNA-Binding Proteins
Drosophila melanogaster
medicine.anatomical_structure
030220 oncology & carcinogenesis
Protein Binding
Signal Transduction
animal structures
Macromolecular Substances
MESH: Drosophila Proteins
Active Transport
Cell Nucleus

Embryonic Structures
MESH: Active Transport
Cell Nucleus

Protein Serine-Threonine Kinases
Biology
MESH: Embryonic Structures
MESH: Protein-Serine-Threonine Kinases
MESH: Drosophila melanogaster
03 medical and health sciences
Mediator
medicine
Animals
MESH: Protein Binding
MESH: Transport Vesicles
Hedgehog Proteins
Transport Vesicles
Hedgehog
030304 developmental biology
Cell Membrane
MESH: Macromolecular Substances
MESH: Hedgehog Proteins
Cell Biology
In vitro
MESH: Kinesin
Smoothened
Nucleus
MESH: DNA-Binding Proteins
Transcription Factors
MESH: Cell Membrane
Zdroj: Nature Cell Biology
Nature Cell Biology, Nature Publishing Group, 2003, 5 (10), pp.907-13. ⟨10.1038/ncb1052⟩
ISSN: 1476-4679
1465-7392
DOI: 10.1038/ncb1052
Popis: International audience; The mechanisms involved in transduction of the Hedgehog (Hh) signal are of considerable interest to developmental and cancer biologists. Stabilization of the integral membrane protein Smoothened (Smo) at the plasma membrane is a crucial step in Hh signalling but the molecular events immediately downstream of Smo remain to be elucidated. We have shown previously that the transcriptional mediator Cubitus interruptus (Ci) is associated in a protein complex with at least two other proteins, the kinesin-like Costal2 (Cos2) and the serine-threonine kinase Fused (Fu). This protein complex governs the access of Ci to the nucleus. Here we show that, consequent on the stabilization of Smo, Cos2 and Fu are destabilized. Moreover, we find that the Cos2-Fu-Ci protein complex is associated with Smo in membrane fractions both in vitro and in vivo. We also show that Cos2 binding on Smo is necessary for the Hh-dependent dissociation of Ci from this complex. We propose that the association of the Cos2 protein complex with Smo at the plasma membrane controls the stability of the complex and allows Ci activation, eliciting its nuclear translocation.
Databáze: OpenAIRE