Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt
Pathway Protein Dishevelled

J 2020

Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled

BERNATÍK, Ondřej; Petra PACLÍKOVÁ; Sri Ranjani GANJI a Vítězslav BRYJA

Základní údaje

Originální název

Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled

Autoři

BERNATÍK, Ondřej; Petra PACLÍKOVÁ; Sri Ranjani GANJI a Vítězslav BRYJA

Vydání

Cells, Basel, MDPI, 2020, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10603 Genetics and heredity

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.600

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/20:00114628

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Smurf2; dishevelled; TGF-beta; BMP signaling; Wnt signaling; prickle; ubiquitination

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 1. 2021 12:35, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body axis, regulation of convergent extension, or development of various organ systems. SMAD ubiquitination regulatory factor (Smurf) family of E3 ubiquitin ligases are important and evolutionary conserved regulators of TGF-beta /BMP signaling pathways. Smurf2 has been previously shown to regulate Wnt/planar cell polarity (PCP) signaling pathway by ubiquitinating Prickle1, one of the key components of PCP. We explored the role of Smurf2 in Wnt pathways in further detail and identified that Smurf2 is also a ubiquitin ligase of Dishevelled (DVL), the key cytoplasmic signal transducer in the Wnt pathway. Interestingly, the Smurf2 and DVL relationship expands beyond substrate-E3 ligase. We can show that DVL activates Smurf2, which allows Smurf2 to ubiquitinate its substrates from Wnt/PCP (Prickle1) as well as TGF-beta /BMP (Smad2) pathways more efficiently. Using SMAD7 as an example of Smurf2 activator we show that DVL and SMAD7 both activates Smurf2 activity. In HEK293 cells the deficiency of DVL phenocopies absence of Smurf2 and leads to the increased phosphorylation of R-Smads. Smurf2-DVL connection provides a novel and intriguing point of crosstalk for Wnt and BMP pathways.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GA15-21789S, projekt VaV

Název: Dishevelled - identifikace základních koordinát

Investor: Grantová agentura ČR, Dishevelled - identifikace základních koordinát

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)

Citovat

BERNATÍK, Ondřej; Petra PACLÍKOVÁ; Sri Ranjani GANJI a Vítězslav BRYJA. Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled. Cells. Basel: MDPI, 2020, roč. 9, č. 5, s. 1-12. ISSN 2073-4409. Dostupné z: https://doi.org/10.3390/cells9051147.

@article{1721436,
   author = {Bernatík, Ondřej and Paclíková, Petra and Ganji, Sri Ranjani and Bryja, Vítězslav},
   article_location = {Basel},
   article_number = {5},
   doi = {https://doi.org/10.3390/cells9051147},
   keywords = {Smurf2; dishevelled; TGF-beta; BMP signaling; Wnt signaling; prickle; ubiquitination},
   language = {eng},
   issn = {2073-4409},
   journal = {Cells},
   title = {Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled},
   url = {https://doi.org/10.3390/cells9051147},
   volume = {9},
   year = {2020}
}

TY  - JOUR
ID  - 1721436
AU  - Bernatík, Ondřej - Paclíková, Petra - Ganji, Sri Ranjani - Bryja, Vítězslav
PY  - 2020
TI  - Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled
JF  - Cells
VL  - 9
IS  - 5
SP  - 1-12
EP  - 1-12
PB  - MDPI
SN  - 20734409
KW  - Smurf2
KW  - dishevelled
KW  - TGF-beta
KW  - BMP signaling
KW  - Wnt signaling
KW  - prickle
KW  - ubiquitination
UR  - https://doi.org/10.3390/cells9051147
L2  - https://doi.org/10.3390/cells9051147
N2  - Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body axis, regulation of convergent extension, or development of various organ systems. SMAD ubiquitination regulatory factor (Smurf) family of E3 ubiquitin ligases are important and evolutionary conserved regulators of TGF-beta /BMP signaling pathways. Smurf2 has been previously shown to regulate Wnt/planar cell polarity (PCP) signaling pathway by ubiquitinating Prickle1, one of the key components of PCP. We explored the role of Smurf2 in Wnt pathways in further detail and identified that Smurf2 is also a ubiquitin ligase of Dishevelled (DVL), the key cytoplasmic signal transducer in the Wnt pathway. Interestingly, the Smurf2 and DVL relationship expands beyond substrate-E3 ligase. We can show that DVL activates Smurf2, which allows Smurf2 to ubiquitinate its substrates from Wnt/PCP (Prickle1) as well as TGF-beta /BMP (Smad2) pathways more efficiently. Using SMAD7 as an example of Smurf2 activator we show that DVL and SMAD7 both activates Smurf2 activity. In HEK293 cells the deficiency of DVL phenocopies absence of Smurf2 and leads to the increased phosphorylation of R-Smads. Smurf2-DVL connection provides a novel and intriguing point of crosstalk for Wnt and BMP pathways.
ER  -

BERNATÍK, Ondřej; Petra PACLÍKOVÁ; Sri Ranjani GANJI a Vítězslav BRYJA. Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled. \textit{Cells}. Basel: MDPI, 2020, roč.~9, č.~5, s.~1-12. ISSN~2073-4409. Dostupné z: https://doi.org/10.3390/cells9051147.

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