ArticleProceedings of the National Academy of Sciences of the United States of America2008
IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- A Systematic Review of Stem Cell Differentiation into Keratinocytes for Regenerative Applications.Stem cell reviews and reports · 2024Pooled it
- Activation of unfolded protein response pathways promotes keratinocyte differentiation and ameliorates psoriasis phenotypes.Cell stress & chaperones · 2026Article
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- Enhancing human NK cell antitumor function by knocking out SMAD4 to counteract TGFβ and activin A suppression.Nature immunology · 2025Article
- Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.Nature communications · 2024Article
- Advances in mesenchymal stem cells therapy for tendinopathies.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Mechanistic Contributions of lncRNAs to Cellular Signaling Pathways Crucial to the Lifecycle of Human Papillomaviruses.Viruses · 2022Review
- A TNFR1-UBCH10 axis drives lung squamous cell carcinoma dedifferentiation and metastasis through a cell-autonomous signaling loop.Cell death & disease · 2022Article
- SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4.Communications biology · 2022Article
- Keratocyte Differentiation Is Regulated by NF-κB and TGFβ Signaling Crosstalk.International journal of molecular sciences · 2022Article
- m6A modification of mRNA in skin diseases.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- OVOL1 inhibits breast cancer cell invasion by enhancing the degradation of TGF-β type I receptor.Signal transduction and targeted therapy · 2022Article
- OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- IKKα-deficient lung adenocarcinomas generate an immunosuppressive microenvironment by overproducing Treg-inducing cytokines.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis.Frontiers in physiology · 2022Article
- Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).Science immunology · 2021Article
- Transforming growth factor beta signaling functions during mammalian kidney development.Pediatric nephrology (Berlin, Germany) · 2021Review
- Naa10p and IKKα interaction regulates EMT in oral squamous cell carcinoma via TGF-β1/Smad pathway.Journal of cellular and molecular medicine · 2021Article
- Transcriptional and signalling regulation of skin epithelial stem cells in homeostasis, wounds and cancer.Experimental dermatology · 2021Review
- Review
35 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
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-cycle exit and differentiation of suprabasal epidermal keratinocytes require nuclear IkappaB kinase alpha (IKKalpha), but not its protein kinase activity. IKKalpha also is a suppressor of squamous cell carcinoma (SCC), but its mode of action remains elusive. Postulating that IKKalpha may serve as a transcriptional regulator in keratinocytes, we searched for cell-cycle-related genes that could illuminate this function. IKKalpha was found to control several Myc antagonists, including Mad1, Mad2, and Ovol1, through the association with TGFbeta-regulated Smad2/3 transcription factors and is required for Smad3 recruitment to at least one of these targets. Surprisingly, Smad2/3-dependent Mad1 induction and keratinocyte differentiation are independent of Smad4, the almost universal coregulator of canonical TGFbeta signaling. IKKalpha also is needed for nuclear accumulation of activated Smad2/3 in the epidermis, and Smad2/3 are required for epidermal differentiation. We suggest that a TGFbeta-Smad2/3-IKKalpha axis is a critical Smad4-independent regulator of keratinocyte proliferation and 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.