ArticleJournal of cellular and molecular medicine2010
Unfolded protein response suppresses CEBPA by induction of calreticulin in acute myeloid leukaemia.
Article in Journal of cellular and molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Endoplasmic Reticulum Stress in Acute Myeloid Leukemia: Pathogenesis, Prognostic Implications, and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Review
- Dyskerin Downregulation Can Induce ER Stress and Promote Autophagy via AKT-mTOR Signaling Deregulation.Biomedicines · 2022Article
- Genetic and Epigenetic Signatures in Acute Promyelocytic Leukemia Treatment and Molecular Remission.Frontiers in genetics · 2022Article
- The Role of the UPR Pathway in the Pathophysiology and Treatment of Bipolar Disorder.Frontiers in cellular neuroscience · 2021Review
- Review
- The ER-localized CaThe Journal of biological chemistry · 2019Article
- Application of a New Multiplexed Array for Rapid, Sensitive, Simultaneous and Quantitative Assessment of Spliced and Unspliced XBP1.Biological procedures online · 2019Article
- Changes of signal transductivity and robustness of gene regulatory network in the carcinogenesis of leukemic subtypes via microarray sample data.Oncotarget · 2018Article
- TUSC3: functional duality of a cancer gene.Cellular and molecular life sciences : CMLS · 2018Review
- The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera.Experimental hematology · 2017Article
- JUN is a key transcriptional regulator of the unfolded protein response in acute myeloid leukemia.Leukemia · 2017Article
- Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study.Chinese medical journal · 2016Article
- Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia.Oncotarget · 2016Article
- Drugging the unfolded protein response in acute leukemias.Journal of hematology & oncology · 2015Review
- Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
- Programmed cell removal: a new obstacle in the road to developing cancer.Nature reviews. Cancer · 2011Review
- Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression.The American journal of pathology · 2011Article
- Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unfolded protein response (UPR) is triggered by the accumulation of misfolded proteins within the endoplasmic reticulum (ER). The role of the UPR during leukemogenesis is unknown so far. Here, we studied the induction of mediators of the UPR in leukaemic cells of AML patients. Increased expression of the spliced variant of the X-box binding protein 1 (XBP1s) was detected in 17.4% (16 of 92) of AML patients. Consistent with activated UPR, this group also had increased expression of ER-resident chaperones such as the 78 kD glucose-regulated protein (GRP78) and of calreticulin. Conditional expression of calreticulin in leukaemic U937 cells was found to increase calreticulin binding to the CEBPA mRNA thereby efficiently blocking translation of the myeloid key transcription factor CEBPA and ultimately affecting myeloid differentiation. Consequently, leukaemic cells from AML patients with activated UPR and thus increased calreticulin levels showed in fact suppressed CEBPA protein expression. We identified two functional ER stress response elements (ERSE) in the calreticulin promoter. The presence of NFY and ATF6, as well as an intact binding site for YY1 within these ERSE motifs were essential for mediating sensitivity to ER stress and activation of calreticulin. Thus, we propose a model of the UPR being activated in a considerable subset of AML patients through induction of calreticulin along the ATF6 pathway, thereby ultimately suppressing CEBPA translation and contributing to the block in myeloid differentiation.
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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.