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DOI | 10.1038/s41467-019-12785-3 |
Itch/beta-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis | |
Infante, Paola1; Faedda, Roberta2; Bernardi, Flavia2; Bufalieri, Francesca2; Severini, Ludovica Lospinoso2; Alfonsi, Romina2; Mazza, Daniela2; Siler, Mariangela2; Coni, Sonia2; Po, Agnese2; Petroni, Marialaura1; Ferretti, Elisabetta3; Mori, Mattia1; De Smaele, Enrico3; Canettieri, Gianluca2,4; Capalbo, Carlo2; Maroder, Marella5; Screpanti, Isabella2; Kool, Marcel6,7,8; Pfister, Stefan M.6,7,8,9; Guardavaccaro, Daniele10,11; Gulino, Alberto2; Di Marcotullio, Lucia2,4 | |
2019-10-22 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Italy; Germany; Netherlands |
英文摘要 | Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/beta-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off. Activation of Hh signalling antagonises the Itch-dependent polyubiquitylation of SuFu. Notably, different SuFu mutations occurring in medulloblastoma patients are insensitive to Itch activity, thus leading to deregulated Hh signalling and enhancing medulloblastoma cell growth. Our findings uncover mechanisms controlling the tumour suppressive functions of SuFu and reveal that their alterations are implicated in medulloblastoma tumorigenesis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000426899000002 |
WOS关键词 | UBIQUITIN LIGASE ; CHILDHOOD MEDULLOBLASTOMA ; TRANSCRIPTION FACTOR ; GORLIN SYNDROME ; BETA-ARRESTINS ; SONIC HEDGEHOG ; GLI ; SUPPRESSOR ; DEGRADATION ; PROTEINS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204609 |
专题 | 资源环境科学 |
作者单位 | 1.Ist Italiano Tecnol, Ctr Life NanoSci Sapienza, I-00161 Rome, Italy; 2.Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy; 3.Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy; 4.Univ Roma La Sapienza, Ist Pasteur Fdn Cenci Bolognetti, I-00161 Rome, Italy; 5.Univ Roma La Sapienza, Dept Med Surg Sci & Biotechnol, I-00161 Rome, Italy; 6.NCT KiTZ, Hopp Childrens Canc Ctr, D-69120 Heidelberg, Germany; 7.German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany; 8.German Canc Consortium DKTK, D-69120 Heidelberg, Germany; 9.Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany; 10.Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands; 11.Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands |
推荐引用方式 GB/T 7714 | Infante, Paola,Faedda, Roberta,Bernardi, Flavia,et al. Itch/beta-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Infante, Paola.,Faedda, Roberta.,Bernardi, Flavia.,Bufalieri, Francesca.,Severini, Ludovica Lospinoso.,...&Di Marcotullio, Lucia.(2019).Itch/beta-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis.NATURE COMMUNICATIONS,9. |
MLA | Infante, Paola,et al."Itch/beta-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis".NATURE COMMUNICATIONS 9(2019). |
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