ArticlePloS one2017
Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Uridine 5'-monophosphate (UMP) synthesis connects nucleotide metabolism to programmed cell death in C. elegans.Cell death and differentiation · 2026Article
- Clinical and Biological Insights into Myelodysplastic Neoplasms Associated with Deletions of Chromosome 5q Region.Hematology reports · 2025Review
- Regulation of reactive oxygen species and the role of mitochondrial apoptotic-related genes in rheumatoid arthritis.Scientific reports · 2025Article
- HSPA9 reduction exacerbates symptoms and cell death in DSS-Induced inflammatory colitis.Scientific reports · 2024Article
- Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.International journal of molecular sciences · 2023Article
- Article
- Proteome Analysis of the Antiproliferative Activity of the Novel Chitooligosaccharide-Gallic Acid Conjugate against the SW620 Colon Cancer Cell Line.Biomedicines · 2023Article
- Increased interaction between endoplasmic reticulum and mitochondria following sleep deprivation.BMC biology · 2023Article
- Emerging Targeted Therapy for Specific Genomic Abnormalities in Acute Myeloid Leukemia.International journal of molecular sciences · 2022Review
- The Hsp70 chaperone system: distinct roles in erythrocyte formation and maintenance.Haematologica · 2021Review
- Haploinsufficiency of multiple del(5q) genes induce B cell abnormalities in mice.Leukemia research · 2020Article
- Characterization of Diabetic and Non-Diabetic Foot Ulcers Using Single-Cell RNA-Sequencing.Micromachines · 2020Article
- Hypomethylating Agent Azacitidine Is Effective in Treating Brain Metastasis Triple-Negative Breast Cancer Through Regulation of DNA Methylation of Keratin 18 Gene.Translational oncology · 2020Article
- TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis.Cell reports · 2020Article
- Article
- Clinical and genetic aspects of defects in the mitochondrial iron-sulfur cluster synthesis pathway.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.Oncotarget · 2018Article
- Modeling Myeloid Malignancies Using Zebrafish.Frontiers in oncology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Myelodysplastic syndromes (MDS) are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis. We show here that HSPA9 knockdown is associated with increased TP53 expression and activity, resulting in increased expression of target genes BAX and p21. HSPA9 protein interacts with TP53 in CD34+ cells and knockdown of HSPA9 increases nuclear TP53 levels, providing a possible mechanism for regulation of TP53 by HSPA9 haploinsufficiency in hematopoietic cells. Concurrent knockdown of TP53 and HSPA9 rescued the increased apoptosis observed in CD34+ cells following knockdown of HSPA9. Reduction of HSPA9 below 50% results in severe inhibition of cell growth, suggesting that del(5q) cells may be preferentially sensitive to further reductions of HSPA9 below 50%, thus providing a genetic vulnerability to del(5q) cells. Treatment of bone marrow cells with MKT-077, an HSPA9 inhibitor, induced apoptosis in a higher percentage of cells from MDS patients with del(5q) compared to non-del(5q) MDS patients and normal donor cells. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to TP53 activation and increased apoptosis observed in del(5q)-associated MDS.
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