Evidence map›Paper›PMID 24086303›Full record

ArticlePloS one2013

The human minor histocompatibility antigen 1 is a RhoGAP.

Bart-Jan de Kreuk, Antje Schaefer, Eloise C Anthony, Simon Tol, Mar Fernandez-Borja, Dirk Geerts, Jos Pool, Lothar Hambach, Els Goulmy, Peter L Hordijk

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

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  5. Fine-Tuned Expression of Evolutionarily Conserved Signaling Molecules in theInternational journal of molecular sciences · 2024
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  7. Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022
    Review
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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

10 authors at 6 institutions in 2 countries.

Bart-Jan de KreukDepartment of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Antje Schaefer
Eloise C Anthony
Simon Tol
Mar Fernandez-Borja
Dirk Geerts
Jos Pool
Lothar Hambach
Els Goulmy
Peter L Hordijk
Academic Medical Center · NLLeiden University Medical Center · NLSanquin · NLUniversity of Amsterdam · NLErasmus MC · NLMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells.

Indexed as

ActinsBase SequenceCell MovementDNA PrimersGTPase-Activating ProteinsHeLa CellsHumansJurkat CellsMinor Histocompatibility AntigensPolymerase Chain ReactionActinsDNA PrimersGTPase-Activating ProteinsMinor Histocompatibility Antigensrho GTPase-activating protein

Identifiers

PMID24086303
PMCPMC3781157
OpenAlexW1994803808

What OpenQuestion 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 OpenQuestion graph.