Dishevelled has a YAP nuclear export function in a tumor
suppressor context-dependent manner

J 2018

Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner

LEE, Y.; N.H. KIM; E.S. CHO; J.H. YANG; Y.H. CHA et al.

Základní údaje

Originální název

Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner

Autoři

Vydání

Nature Communications, London, Nature Publishing Group, 2018, 2041-1723

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.878

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/18:00101504

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

ACTIVATED PROTEIN-KINASE; PLANAR CELL POLARITY; ORGAN SIZE CONTROL; HIPPO PATHWAY; BETA-CATENIN; ENERGY STRESS; CONTACT INHIBITION; SIGNALING-PATHWAY; CANCER; LKB1

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 4. 2024 13:02, Mgr. Michal Petr

Anotace

V originále

Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with an increase in TEAD transcriptional activity. DVL is also required for YAP subcellular localization induced by E-cadherin, a-catenin, or AMPK activation. Importantly, the nuclear-cytoplasmic trafficking is dependent on the p53-Lats2 or LKB1-AMPK tumor suppressor axes, which determine YAP phosphorylation status. In vivo and clinical data support that the loss of p53 or LKB1 relieves DVL-linked reciprocal inhibition between the Wnt and nuclear YAP activity. Our observations provide mechanistic insights into controlled proliferation coupled with epithelial polarity during development and human cancer.

Návaznosti

GA17-16680S, projekt VaV

Název: Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)

Investor: Grantová agentura ČR, Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)

GA18-17658S, projekt VaV

Název: Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled

Investor: Grantová agentura ČR, Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled

Citovat

LEE, Y.; N.H. KIM; E.S. CHO; J.H. YANG; Y.H. CHA; H.E. KANG; J.S. YUN; S.B. CHO; S.H. LEE; Petra PACLÍKOVÁ; Tomasz Witold RADASZKIEWICZ; Vítězslav BRYJA; C.G. KANG; Y.S. YUK; S.Y. CHA; S.Y. KIM; H.S. KIM a J.I. YOOK. Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner. Nature Communications. London: Nature Publishing Group, 2018, roč. 9, č. 1, s. 1-16. ISSN 2041-1723. Dostupné z: https://doi.org/10.1038/s41467-018-04757-w.

@article{1483380,
   author = {Lee, Y. and Kim, N.H. and Cho, E.S. and Yang, J.H. and Cha, Y.H. and Kang, H.E. and Yun, J.S. and Cho, S.B. and Lee, S.H. and Paclíková, Petra and Radaszkiewicz, Tomasz Witold and Bryja, Vítězslav and Kang, C.G. and Yuk, Y.S. and Cha, S.Y. and Kim, S.Y. and Kim, H.S. and Yook, J.I.},
   article_location = {London},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41467-018-04757-w},
   keywords = {ACTIVATED PROTEIN-KINASE; PLANAR CELL POLARITY; ORGAN SIZE CONTROL; HIPPO PATHWAY; BETA-CATENIN; ENERGY STRESS; CONTACT INHIBITION; SIGNALING-PATHWAY; CANCER; LKB1},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner},
   url = {https://www.nature.com/articles/s41467-018-04757-w},
   volume = {9},
   year = {2018}
}

TY  - JOUR
ID  - 1483380
AU  - Lee, Y. - Kim, N.H. - Cho, E.S. - Yang, J.H. - Cha, Y.H. - Kang, H.E. - Yun, J.S. - Cho, S.B. - Lee, S.H. - Paclíková, Petra - Radaszkiewicz, Tomasz Witold - Bryja, Vítězslav - Kang, C.G. - Yuk, Y.S. - Cha, S.Y. - Kim, S.Y. - Kim, H.S. - Yook, J.I.
PY  - 2018
TI  - Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner
JF  - Nature Communications
VL  - 9
IS  - 1
SP  - 1-16
EP  - 1-16
PB  - Nature Publishing Group
SN  - 20411723
KW  - ACTIVATED PROTEIN-KINASE
KW  - PLANAR CELL POLARITY
KW  - ORGAN SIZE CONTROL
KW  - HIPPO PATHWAY
KW  - BETA-CATENIN
KW  - ENERGY STRESS
KW  - CONTACT INHIBITION
KW  - SIGNALING-PATHWAY
KW  - CANCER
KW  - LKB1
UR  - https://www.nature.com/articles/s41467-018-04757-w
N2  - Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with an increase in TEAD transcriptional activity. DVL is also required for YAP subcellular localization induced by E-cadherin, a-catenin, or AMPK activation. Importantly, the nuclear-cytoplasmic trafficking is dependent on the p53-Lats2 or LKB1-AMPK tumor suppressor axes, which determine YAP phosphorylation status. In vivo and clinical data support that the loss of p53 or LKB1 relieves DVL-linked reciprocal inhibition between the Wnt and nuclear YAP activity. Our observations provide mechanistic insights into controlled proliferation coupled with epithelial polarity during development and human cancer.
ER  -

LEE, Y.; N.H. KIM; E.S. CHO; J.H. YANG; Y.H. CHA; H.E. KANG; J.S. YUN; S.B. CHO; S.H. LEE; Petra PACLÍKOVÁ; Tomasz Witold RADASZKIEWICZ; Vítězslav BRYJA; C.G. KANG; Y.S. YUK; S.Y. CHA; S.Y. KIM; H.S. KIM a J.I. YOOK. Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner. \textit{Nature Communications}. London: Nature Publishing Group, 2018, roč.~9, č.~1, s.~1-16. ISSN~2041-1723. Dostupné z: https://doi.org/10.1038/s41467-018-04757-w.

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