Evidence map›Paper›PMID 30686098›Full record

ArticleAutophagy2019

Ubiquitination of UVRAG by SMURF1 promotes autophagosome maturation and inhibits hepatocellular carcinoma growth.

Xing Feng, Yanyan Jia, Yuyu Zhang, Fei Ma, Yuekun Zhu, Xuehui Hong, Qingxin Zhou, Ruixing He, Heng Zhang, Junfei Jin and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 121 citations in OpenAlex.

  1. Review
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  14. Autophagy activation by the Becn1Brain, behavior, and immunity · 2026
    Article
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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 2 countries.

Xing Fenga The affiliated Hospital of Guilin Medical University , Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guangxi Neurological Diseases Clinical Research Center , Guilin , Guangxi , China.ORCID 0000-0001-8226-3389
Yanyan Jiac Department of Pharmacy , Xijing Hospital, Fourth Military University , Xi' an , Shanxi , China.
Yuyu Zhangd Department of Radiation Oncology , The First Hospital of Jilin University , Changchun , China.
Fei Mae Department of General Surgery , the Second Affiliated Hospital of Harbin Medical University , Harbin , Heilongjiang , China.
Yuekun Zhuf Department of General Surgery , The First Affiliated Hospital of Harbin Medical University , Harbin , Heilongjiang , China.
Xuehui Hongg Department of Gastrointestinal Surgery , Zhongshan Hospital of Xiamen University, Institute of Gastrointestinal Oncology, Medical College of Xiamen University , Xiamen , Fujian , China.
Qingxin Zhouh Department of Gastrointestinal Oncology , Harbin Medical University Cancer Hospital , Harbin , Heilongjiang , China.
Ruixing Hei Department of Clinical Medicine , West China University of Medical Science , Chengdu , Sichuan , China.
Heng Zhangj Department of Histology and Embryology , Xiang Ya School of Medicine, Central South University , Changsha , Hunan , China.
Junfei Jink Laboratory of Hepatobiliary and Pancreatic Surgery , Affiliated Hospital of Guilin Medical University , Guilin , Guangxi 541001 , China.
Daxun Piaof Department of General Surgery , The First Affiliated Hospital of Harbin Medical University , Harbin , Heilongjiang , China.
He Huangj Department of Histology and Embryology , Xiang Ya School of Medicine, Central South University , Changsha , Hunan , China.
Qinghua Lia The affiliated Hospital of Guilin Medical University , Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guangxi Neurological Diseases Clinical Research Center , Guilin , Guangxi , China.
Xingfeng Qiun Department of Gastrointestinal Surgery , Zhongshan Hospital of Xiamen University , Xiamen , Fujian , China.
Zhiyong Zhanga The affiliated Hospital of Guilin Medical University , Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guangxi Neurological Diseases Clinical Research Center , Guilin , Guangxi , China.ORCID 0000-0001-8576-1607
Harbin Medical University · CNCentral South University · CNGuilin Medical University · CNRutgers, The State University of New Jersey · USZhongshan Hospital of Xiamen University · CNJilin University · CNWest China Medical Center of Sichuan University · CNXijing Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

UVRAG (UV radiation resistance associated) is an important regulator of mammalian macroautophagy/autophagy by interacting with BECN1, PIK3C3, and RUBCN. Phosphorylation of UVRAG by MTORC1 negatively regulates autophagosome maturation under nutrient-enriched conditions. However, how UVRAG ubiquitination is regulated is still unknown. Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux. We also demonstrate that CSNK1A1-mediated UVRAG phosphorylation at Ser522 disrupts the binding of SMURF1 to UVRAG through PPxY motif and blocks UVRAG ubiquitination-mediated autophagosome maturation. Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity. Importantly, we provide

Indexed as

UbiquitinationAmino Acid MotifsAnimalsAutophagosomesCarcinoma, HepatocellularCasein Kinase IalphaDeubiquitinating EnzymesEndopeptidasesErbB ReceptorsHEK293 CellsHumansLiver NeoplasmsMiceMice, Inbred BALB CMice, NudeMutationCasein Kinase IalphaCSNK1A1 protein, humanDeubiquitinating EnzymesEGFR protein, humanEndopeptidasesErbB ReceptorsSMURF1 protein, humanTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUbiquitin ThiolesteraseUVRAG protein, humanZRANB1 protein, humanCSNK1A1/CK1αphosphorylationSMURF1ubiquitinationUVRAGZRANB1/TRABID

Identifiers

PMID30686098
PMCPMC6613838
OpenAlexW2912309278

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.