ArticlePloS one2010
Nucleo-cytoplasmic localization domains regulate Krüppel-like factor 6 (KLF6) protein stability and tumor suppressor function.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Molecular mechanisms underlying the inhibition of cell migration and invasion in endometriosis: Advances in pharmacological research (Review).Biomedical reports · 2025Review
- Molecular function of Krüppel-like factor 7 in biology.Acta biochimica et biophysica Sinica · 2023Review
- KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Prostate cancer: Alternatively spliced mRNA transcripts in tumor progression and their uses as therapeutic targets.The international journal of biochemistry & cell biology · 2021Review
- MiR-181d-5p Targets KLF6 to Improve Ischemia/Reperfusion-Induced AKI Through Effects on Renal Function, Apoptosis, and Inflammation.Frontiers in physiology · 2020Article
- [Nucleus translocation of membrane/cytoplasm proteins in tumor cells].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Article
- Nuclear Klf4 accumulation is associated with cetuximab drug-resistance and predicts poor prognosis of nasopharyngeal carcinoma.Journal of translational medicine · 2018Article
- Krüppel-like factors: Crippling and un-crippling metabolic pathways.JACC. Basic to translational science · 2018Article
- Article
- KLF6 depletion promotes NF-κB signaling in glioblastoma.Oncogene · 2017Article
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- Ah Receptor Pathway Intricacies; Signaling Through Diverse Protein Partners and DNA-Motifs.Toxicology research · 2015Article
- Krüppel-like factor 6 is a co-activator of NF-κB that mediates p65-dependent transcription of selected downstream genes.The Journal of biological chemistry · 2014Article
- Article
- GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21.Oncogene · 2013Article
- The tumor suppressor Kruppel-like factor 6 is a novel aryl hydrocarbon receptor DNA binding partner.The Journal of pharmacology and experimental therapeutics · 2013Article
- The reproductive phenotype of mice null for transcription factor Krüppel-like factor 13 suggests compensatory function of family member Krüppel-like factor 9 in the peri-implantation uterus.Biology of reproduction · 2012Article
- Enhanced hepatocarcinogenesis in mouse models and human hepatocellular carcinoma by coordinate KLF6 depletion and increased messenger RNA splicing.Hepatology (Baltimore, Md.) · 2012Article
- KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation.The American journal of pathology · 2012Article
- Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe tumor suppressor KLF6 and its oncogenic cytoplasmic splice variant KLF6-SV1 represent a paradigm in cancer biology in that their antagonistic cancer functions are encoded within the same gene. As a consequence of splicing, KLF6-SV1 loses both the C-terminus C2H2 three zinc finger (ZF) domain, which characterizes all KLF proteins, as well as the adjacent 5' basic region (5BR), a putative nuclear localization signal (NLS). It has been hypothesized that this NLS is a functional domain critical to direct the distinct subcellular localization of the tumor suppressor and its splice variant. METHODOLOGY/PRINCIPAL
findingsIn this study, we demonstrate using EGFP fusion constructs that KLF6/KLF6-SV1 nucleo-cytoplasmic transport is not regulated by the 5' basic region but activated by a novel NLS encoded within the ZF domain, and a nuclear export signal (NES) located in the first 16 amino acids of the shared N-terminus sequence. We demonstrate KLF6 nuclear export to be Crm1-dependent. The dysregulation of nucleo-cytoplasmic transport when disrupting the KLF6 NLS using site-directed mutagenesis showed that its integrity is necessary for appropriate protein stability. Moreover, these mutations impaired transcriptional induction of two KLF6 well-characterized target genes, E-cadherin and p21, as shown by RT-PCR and luciferase promoter assays. The addition of the ZF domain to KLF6-SV1 results in its nuclear localization and a markedly decreased half-life similar to wild type KLF6. CONCLUSIONS/SIGNIFICANCE: We describe the domains that control KLF6 nucleo-cytoplasmic shuttling and how these domains play a role in KLF6 protein half-life and tumor suppressor function. The results begin to mechanistically explain, at least in part, the opposing functions of KLF6 and KLF6-SV1 in cancer.
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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.