Evidence map›Paper›PMID 22807448›Full record

ArticleThe Journal of biological chemistry2012

The GTPase-deficient Rnd proteins are stabilized by their effectors.

Liuh Ling Goh, Ed Manser

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. The small GTPase MRAS is a broken switch.Nature communications · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis.International journal of molecular sciences · 2019
    Review
  8. RND1 is up-regulated in esophageal squamous cell carcinoma and promotes the growth and migration of cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  9. Pathophysiological Functions of Rnd3/RhoE.Comprehensive Physiology · 2015
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
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

2 authors at 1 institution in 1 country.

Liuh Ling GohRho GTPases Signaling Group, Institute of Medical Biology, 8A Biomedical Grove, 06-06 Immunos Building 138648, Singapore.
Ed Manser
Institute of Medical Biology · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rnd proteins are Rho family GTP-binding proteins with cellular functions that antagonize RhoA signaling. We recently described a new Rnd3 effector Syx, also named PLEKHG5, that interacts with Rnds via a Raf1-like "Ras-binding domain." Syx is a multidomain RhoGEF that participates in early zebrafish development. Here we demonstrated that Rnd1, Rnd2, and Rnd3 stability is acutely dependent on interaction with their effectors such as Syx or p190 RhoGAP. Although Rnd3 turnover is blocked by treatment of cells with MG132, we provide evidence that such turnover is mediated indirectly by effects on the Rnd3 effectors, rather than on Rnd3 itself, which is not significantly ubiquitinated. The minimal regions of Syx and p190 RhoGAP that bind Rnd3 are not sequence-related but have similar effects. We have identified features that allow for Rnd3 turnover including a conserved Lys-45 close to the switch I region and the C-terminal membrane-binding domain of Rnd3, which cannot be substituted by the equivalent Cdc42 CAAX sequence. By contrast, an effector binding-defective mutant of Rnd3 when overexpressed undergoes turnover at normal rates. Interestingly the activity of the RhoA-regulated kinase ROCK stimulates Rnd3 turnover. This study suggests that Rnd proteins are regulated through feedback mechanisms in cells where the level of effectors and RhoA activity influence the stability of Rnd proteins. This effector feedback behavior is analogous to the ability of ACK1 and PAK1 to prolong the lifetime of the active GTP-bound state of Cdc42 and Rac1.

Indexed as

Animalscdc42 GTP-Binding ProteinChlorocebus aethiopsCOS CellsCysteine Proteinase InhibitorsEnzyme StabilityGuanine Nucleotide Exchange FactorsHEK293 CellsHeLa CellsHumansLeupeptinsMutationp21-Activated KinasesProtein Structure, TertiaryProtein-Tyrosine Kinasesrac1 GTP-Binding ProteinARHGAP35 protein, humanbenzyloxycarbonylleucyl-leucyl-leucine aldehydecdc42 GTP-Binding ProteinCysteine Proteinase InhibitorsGuanine Nucleotide Exchange FactorsLeupeptinsp21-Activated KinasesPAK1 protein, humanProtein-Tyrosine Kinasesrac1 GTP-Binding ProteinRAC1 protein, humanRepressor Proteinsrho-Associated Kinasesrho GTP-Binding ProteinsTNK2 protein, human

Identifiers

PMID22807448
PMCPMC3442376
OpenAlexW2079764850

What OpenQuestion holds

Textmetadata
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.