KLF9 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | KLF9 , BTEB, BTEB1, Kruppel-like factor 9, Kruppel like factor 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 602902 MGI: 1333856 HomoloGene: 931 GeneCards: KLF9 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Krueppel-like factor 9 is a protein that in humans is encoded by the KLF9 gene. [5] [6] Previously known as Basic Transcription Element Binding Protein 1 (BTEB Protein 1), Klf9 is part of the Sp1 C2H2-type zinc finger family of transcription factors. Several previous studies showed Klf9-related regulation of animal development, including cell differentiation of B cells, keratinocytes, and neurons. [7] Klf9 is also a key transcriptional regulator for uterine endometrial cell proliferation, adhesion, and differentiation, all factors that are essential during the process of pregnancy and are turned off during tumorigenesis. [8]
The protein encoded by this gene is a transcription factor that binds to GC box elements located in the promoter. Binding of the encoded protein to a single GC box inhibits mRNA expression while binding to tandemly repeated GC box elements activates transcription. [6]
Oxidative stress increases expression of Klf9 and overexpression of Klf9 gene sensitizes the cell to oxidative stress and reactive oxygen species (ROS).
Using a short hairpin RNA (shRNA) to silence expression of Klf9 provides resistance for the cell to oxidative stress and ROS-related cell death. Klf9 is upregulated by ROS and promotes ROS-related cell death. [7]
Klf9 exhibits similarities to other known oxidative stress genes like NQO1 and HMOX1. When exposed to the same amount of hydrogen peroxide, both mouse embryo cells and human cells produced similar amounts of Klf9 and NQO1/HMOX. [7] The opposite of this effect also occurs; Klf9 overexpression within the cell leads to an increase in intracellular ROS. The result of the increase in intracellular ROS and Klf9 is increase in cell death; with the overexpressed Klf9 gene, more cells die. Similar cell death was found in vivo when wild-type mice were exposed to oxidative stress agent paraquat intranasally, which validated the oxidative stress-dependent Klf9 expression found in just the cell lines. [7]
Regions around 10 kb upstream and 1 kb downstream of Klf9 transcription start site contain conserved antioxidant response elements (AREs), which are binding sites for Nrf2. [7] Nrf2 is a major regulator of the antioxidant response to ROS within the cell. Klf9 is upregulated by Nrf2; when oxidative stress is high and concentration of intracellular ROS is high, Nrf2 binds to Klf9 promoter, which increases the amount of intracellular ROS, leading to cell death. When oxidative stress is low, Nrf2 goes through its normal pathway by increasing the amount of antioxidant species within the cell and decreasing the amount of intracellular ROS. [7]
A Klf9 deficiency suppresses bleomycin-induced fibrosis in the lungs of mice. By introducing bleomycin to lung tissue, the tissue will produce ROS and develop fibrotic lung tissue to combat the damage done by the bleomycin. When Klf9 was knocked out in these mice, not as much fibrotic lung tissue was formed. [7] Because of this finding, the researchers proposed that manipulations of Klf9 levels within the body may be a valid treatment for other diseases as well, including certain types of cancer. [7]
KLF9 has been shown to interact with progesterone receptor. [9]
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of eukaryotic C2H2 zinc finger DNA-binding proteins that regulate gene expression. This family has been expanded to also include the Sp transcription factor and related proteins, forming the Sp/KLF family.
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.
The aryl-hydrocarbon receptor repressor also known as AHRR is a human gene.
Jun dimerization protein 2 (JUNDM2) is a protein that in humans is encoded by the JDP2 gene. The Jun dimerization protein is a member of the AP-1 family of transcription factors.
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
Krueppel-like factor 6 is a protein that in humans is encoded by the KLF6 gene.
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.
Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).
Endothelial PAS domain-containing protein 1 is a protein that is encoded by the EPAS1 gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart. Mutation often leads to neuroendocrine tumors.
Krueppel-like factor 5 is a protein that in humans is encoded by the KLF5 gene.
Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the Keap1 gene.
Hepatic leukemia factor is a protein that in humans is encoded by the HLF gene.
Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.
Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1).
Kruppel-like factor 13, also known as KLF13, is a protein that in humans is encoded by the KLF13 gene.
Krueppel-like factor 12 is a protein that in humans is encoded by the KLF12 gene.
HBx is a hepatitis B viral protein. It is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host. It forms a heterodimeric complex with its cellular target protein, and this interaction dysregulates centrosome dynamics and mitotic spindle formation. It interacts with DDB1 redirecting the ubiquitin ligase activity of the CUL4-DDB1 E3 complexes, which are intimately involved in the intracellular regulation of DNA replication and repair, transcription and signal transduction.
Krüppel-like factor 15 is a protein that in humans is encoded by the KLF15 gene in the Krüppel-like factor family. Its former designation KKLF stands for kidney-enriched Krüppel-like factor.
Kruppel like factor 16 is a protein that in humans is encoded by the KLF16 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.