ArticleArteriosclerosis, thrombosis, and vascular biology2011
Platelet protein kinase C-theta deficiency with human RUNX1 mutation: PRKCQ is a transcriptional target of RUNX1.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency.Blood advances · 2024Article
- An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment.International journal of molecular sciences · 2023Review
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- Defective RAB1B-related megakaryocytic ER-to-Golgi transport in RUNX1 haplodeficiency: impact on von Willebrand factor.Blood advances · 2018Article
- Transcription Factor RUNX1 Regulates PlateletCirculation · 2017Article
- Defective acid hydrolase secretion in RUNX1 haplodeficiency: Evidence for a global platelet secretory defect.Haemophilia : the official journal of the World Federation of Hemophilia · 2017Article
- Hematopoietic transcription factor mutations: important players in inherited platelet defects.Blood · 2017Review
- Dysregulation of PLDN (pallidin) is a mechanism for platelet dense granule deficiency in RUNX1 haplodeficiency.Journal of thrombosis and haemostasis : JTH · 2017Article
- Review
- Hematopoietic transcription factor mutations and inherited platelet dysfunction.F1000prime reports · 2015Review
- Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome.Leukemia research reports · 2015Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMutations in the hematopoietic transcription factor RUNX1 cause thrombocytopenia and impaired platelet function. In a patient with a heterozygous mutation in RUNX1, we have described decreased platelet pleckstrin phosphorylation and protein kinase C- (PKC-, gene PRKCQ) associated with thrombocytopenia, impaired platelet aggregation, and dense granule secretion. Little is known regarding regulation of PKC- in megakaryocytes and platelets. We have addressed the hypothesis that PRKCQ is a direct transcriptional target of RUNX1. METHODS AND
resultsIn a chromatin immunoprecipitation assay using megakaryocytic cells, there was RUNX1 binding in vivo to PRKCQ promoter region -1225 to -1056 bp containing a RUNX1 consensus site ACCGCA at -1088 to -1069 bp; an electrophoretic mobility shift assay showed RUNX1 binding to the specific site. In RUNX1 overexpression studies, PKC- protein expression and promoter activity were enhanced; mutation of RUNX1 site showed decreased activity even with RUNX1 overexpression. Lastly, PRKCQ promoter activity and PKC- protein were decreased by short interfering RNA knockdown of RUNX1.
conclusionsOur results provide the first evidence that PRKCQ is regulated at the transcriptional level by RUNX1 in megakaryocytic cells and a mechanism for PKC- deficiency associated with RUNX1 haplodeficiency.
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Registered trials
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.