ArticleMolecular and cellular biology1999
The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 354 citations in OpenAlex.
- Pooled it
- The multifaceted role of mitochondria in autism spectrum disorder.Molecular psychiatry · 2025Review
- Review
- Down-regulation of MIR-378A-3P expression associated with inflammation: The effects of restoring its levels.PloS one · 2025Article
- Capivasertib reverses chemotherapy-induced esophageal cancer resistance via inhibiting Akt-associated Mcl-1 upregulation.Heliyon · 2024Article
- Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma.Cell death discovery · 2024Article
- Evaluation of the in vitro human skin percutaneous absorption of ketoprofen in topical anhydrous and aqueous gels.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024Review
- miR-142: A Master Regulator in Hematological Malignancies and Therapeutic Opportunities.Cells · 2023Review
- Article
- Augmenting Venetoclax Activity Through Signal Transduction in AML.Journal of cellular signaling · 2023Article
- Circ-CREBBP inhibits sperm apoptosis via the PI3K-Akt signaling pathway by sponging miR-10384 and miR-143-3p.Communications biology · 2022Article
- Elp3-mediated codon-dependent translation promotes mTORC2 activation and regulates macrophage polarization.The EMBO journal · 2022Article
- Evaluation of an Anhydrous Permeation-Enhancing Vehicle for Percutaneous Absorption of Hormones.AAPS PharmSciTech · 2022Article
- Targeting Orphan G Protein-Coupled Receptor 17 with T0 Ligand Impairs Glioblastoma Growth.Cancers · 2021Article
- Article
- Review
- Review
- Targeting of PI3K/AKT signaling and DNA damage response in acute myeloid leukemia: a novel therapeutic strategy to boost chemotherapy response and overcome resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma.Frontiers in pharmacology · 2021Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) signaling pathways and plays an important role in the viability response of these cytokines. In this study, we demonstrated that cytokine stimulation of mcl-1 mRNA and protein expression were attenuated by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-K) inhibitors. Reporter gene assays further showed that the PI3-K/Akt signaling pathway was involved in IL-3 activation of mcl-1 gene transcription. Analysis of the mcl-1 promoter revealed that both promoter elements, SIE at position -87 and CRE-2 at -70, contribute to IL-3 stimulation of mcl-1 gene expression. Although either the SIE site or the CRE-2 site alone was sufficient to confer IL-3 inducibility on a heterologous promoter, only IL-3 activation of the CRE-2 reporter was mediated via the PI3-K/Akt pathway. The SIE binding activity was constitutively high in cells deprived of or stimulated by IL-3. In contrast, the CRE-2 binding activity was low in cytokine-starved cells and was strongly induced within 1 h following cytokine treatment of cells. In addition, cytokine induction of the CRE-2 but not of the SIE binding activity was dependent on activation of the PI3-K/Akt signaling pathway. Lastly, we showed that CREB was one component of the CRE-2 binding complex and played a role in IL-3 activation of the mcl-1 reporter gene. Taken together, our results suggest that both PI3-K/Akt-dependent and -independent pathways contribute to the IL-3 activation of mcl-1 gene expression. Activation of mcl-1 by the PI3-K/Akt-dependent pathway is through a transcription factor complex containing CREB.
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