Evidence map›Paper›PMID 39322015›Full record

ArticleThe Journal of biological chemistry2024

Stub1 promotes degradation of the activated Diaph3: A negative feedback regulatory mechanism of the actin nucleator.

Cui Qiu, Linqing Zhang, Chenxuan Yong, Ruixing Hu, Yuecen Sun, Busong Wang, Lei Fang, Guang-Jie Zhu, Qing Lu, Junguo Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. A Structural Variant in the 5' Regulatory Region ofInternational archives of otorhinolaryngology · 2026
    Article
  2. Article
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

13 authors.

Cui QiuMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Linqing ZhangMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Chenxuan YongMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Ruixing HuBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
Yuecen SunMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Busong WangState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Medical School, Nanjing University, Nanjing, China.
Lei FangState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Medical School, Nanjing University, Nanjing, China.
Guang-Jie ZhuMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China; Research Institute of Otolaryngology, Nanjing, China.
Qing LuBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
Junguo WangMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China; Research Institute of Otolaryngology, Nanjing, China. Electronic address: wangjunguo2821@163.com.
Xiaofeng MaMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China; Research Institute of Otolaryngology, Nanjing, China. Electronic address: mxfent@126.com.
Luping ZhangDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Hospital, Nantong University, Nantong, China. Electronic address: zhanglp910@126.com.
Guoqiang WanMOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Medical School, Nanjing University, Nanjing, China; Research Institute of Otolaryngology, Nanjing, China. Electronic address: guoqiangwan@nju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The formin protein Diaph3 is an actin nucleator that regulates numerous cytoskeleton-dependent cellular processes through the activation of actin polymerization. Expression and activity of Diaph3 is tightly regulated: lack of Diaph3 results in developmental defects and embryonic lethality in mice, while overexpression of Diaph3 causes auditory neuropathy. It is known that Diaph3 homophilic interactions include the intramolecular interaction of its Dia-inhibitory domain (DID)-diaphanous autoregulatory domain (DAD) domains and the intermolecular interactions of DD-DD domains or FH2-FH2 domains. However, the physiological significance of these interactions in Diaph3 protein stability and activity is not fully understood. In this study, we show that FH2-FH2 interaction promotes Diaph3 activity, while DID-DAD and DD-DD interactions inhibit Diaph3 activity through distinct mechanisms. DID-DAD interaction is responsible for the autoinhibition of Diaph3 protein, which is disrupted by binding of Rho GTPases. Interestingly, we find that DID-DAD interaction stabilizes the expression of each DID or DAD domain against proteasomal-mediated degradation. Disruption of DID-DAD interaction by RhoA binding or M1041A mutation causes increased Diaph3 activity and accelerated degradation of the activated Diaph3 protein. Further, the activated Diaph3 is ubiquitinated at K1142/1143/1144 lysine residues by the E3 ligase Stub1. Expression of Stub1 is causally related to the stability and activity of Diaph3. Knockdown of Stub1 in mouse cochlea results in hair cell stereocilia defects, neuronal degeneration, and hearing loss, resembling the phenotypes of mice overexpressing Diaph3. Thus, our study reports a novel regulatory mechanism of Diaph3 protein expression and activity whereby the active but not inactive Diaph3 is readily degraded to prevent excessive actin polymerization.

Indexed as

ForminsUbiquitin-Protein LigasesActinsAdaptor Proteins, Signal TransducingAnimalsFeedback, PhysiologicalHEK293 CellsHumansMiceProtein DomainsProteolysisrhoA GTP-Binding ProteinActinsAdaptor Proteins, Signal TransducingDIAPH3 protein, humanDiaph3 protein, mouseForminsrhoA GTP-Binding ProteinStub1 protein, mouseUbiquitin-Protein Ligasesactin polymerizationautoinhibitionDiaph3hearing lossnegative feedbackprotein stabilityStub1

Identifiers

PMID39322015
PMCPMC11736009

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.