ArticleBlood2002
The Stat5-RARalpha fusion protein represses transcription and differentiation through interaction with a corepressor complex.
Article in Blood, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 39 citations in OpenAlex.
- Defined Human Leukemic CD34+ Liquid Cultures to Study HDAC/Transcriptional Repressor Complexes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Current views on the genetic landscape and management of variant acute promyelocytic leukemia.Biomarker research · 2021Review
- Emerging therapeutic paradigms to target the dysregulated Janus kinase/signal transducer and activator of transcription pathway in hematological malignancies.Leukemia & lymphoma · 2014Review
- Article
- STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.Leukemia · 2014Review
- Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application.Biomarker research · 2013Article
- Transcription factor Stat5a/b as a therapeutic target protein for prostate cancer.The international journal of biochemistry & cell biology · 2010Review
- Targeting signal transducer and activator of transcription signaling pathway in leukemias.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Review
- Signal transducer and activator of transcription 5A/B in prostate and breast cancers.Endocrine-related cancer · 2008Review
- Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity.Molecular and cellular biology · 2004Article
- Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma.The Journal of experimental medicine · 2003Article
- The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2.The EMBO journal · 2003Article
- Deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5.Molecular and cellular biology · 2003Article
- Variations on a theme: the alternate translocations in APL.Leukemia · 2002Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor Stat5 mediates the cellular response to activation of multiple cytokine receptors involved in the regulation of proliferation and differentiation of hematopoietic cells. Recently, the human Stat5 gene was found to be translocated to the RARalpha gene in a patient with acute promyelocytic leukemia indicating that Stat5 might also play a role in cellular transformation. We investigated the mechanism by which Stat5 might exert this function and studied the biochemical and cellular functions of fusion proteins comprising Stat5 and RARalpha. The expression of Stat5-RARalpha causes the transcriptional repression of gene transcription, a process that requires the coiled-coil domain of Stat5 (amino acid positions 133-333). Oligomerization of this domain in the Stat5-RARalpha fusion protein leads to stable binding of the corepressor SMRT independent of all-trans retinoic acid (ATRA) stimulation and is accompanied by an impaired response to differentiation signals in hematopoietic cells. This inhibitory effect on myeloid differentiation cannot be overcome by simultaneous coexpression of RARalpha. We conclude that Stat5 is capable of interacting with a corepressor complex that alters the pattern of corepressor binding to RARalpha and its dissociation in response to ATRA stimulation, leading to enhanced repressor activity and a block of hematopoietic differentiation.
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