KLF9

Last updated
KLF9
Identifiers
Aliases KLF9 , BTEB, BTEB1, Kruppel-like factor 9, Kruppel like factor 9
External IDs OMIM: 602902 MGI: 1333856 HomoloGene: 931 GeneCards: KLF9
Orthologs
SpeciesHumanMouse
Entrez

687

16601

Ensembl

ENSG00000119138

ENSMUSG00000033863

UniProt

Q13886

O35739
Q8CEC4

RefSeq (mRNA)

NM_001206

NM_010638

RefSeq (protein)

NP_001197

NP_034768

Location (UCSC) Chr 9: 70.38 – 70.41 Mb Chr 19: 23.12 – 23.15 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

Function

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]

Animal studies

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]

Interactions

KLF9 has been shown to interact with progesterone receptor. [9]

Related Research Articles

<span class="mw-page-title-main">Progesterone receptor</span> Cytoplasmic receptor protein found inside cells

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.

<span class="mw-page-title-main">Aryl hydrocarbon receptor nuclear translocator</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Jun dimerization protein</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

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.

<span class="mw-page-title-main">KLF6</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 6 is a protein that in humans is encoded by the KLF6 gene.

<span class="mw-page-title-main">NRF1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">KLF4</span> Protein-coding gene in the species Homo sapiens

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).

<span class="mw-page-title-main">EPAS1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">KLF5</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 5 is a protein that in humans is encoded by the KLF5 gene.

<span class="mw-page-title-main">KEAP1</span> Protein-coding gene in the species Homo sapiens

Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the Keap1 gene.

<i>HLF</i> (gene) Protein-coding gene in the species Homo sapiens

Hepatic leukemia factor is a protein that in humans is encoded by the HLF gene.

<span class="mw-page-title-main">MAFG</span> Protein-coding gene in the species Homo sapiens

Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.

<span class="mw-page-title-main">NFE2L1</span> Protein-coding gene in the species Homo sapiens

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).

<span class="mw-page-title-main">KLF13</span> Protein-coding gene in the species Homo sapiens

Kruppel-like factor 13, also known as KLF13, is a protein that in humans is encoded by the KLF13 gene.

<span class="mw-page-title-main">KLF12</span> Protein-coding gene in the species Homo sapiens

Krueppel-like factor 12 is a protein that in humans is encoded by the KLF12 gene.

<span class="mw-page-title-main">HBx</span>

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.

<span class="mw-page-title-main">KLF15</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Kruppel like factor 16</span> Protein-coding gene in the species Homo sapiens

Kruppel like factor 16 is a protein that in humans is encoded by the KLF16 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000119138 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033863 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Imataka H, Sogawa K, Yasumoto K, Kikuchi Y, Sasano K, Kobayashi A, Hayami M, Fujii-Kuriyama Y (Nov 1992). "Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene". EMBO J. 11 (10): 3663–71. doi:10.1002/j.1460-2075.1992.tb05451.x. PMC   556826 . PMID   1356762.
  6. 1 2 "Entrez Gene: KLF9 Kruppel-like factor 9".
  7. 1 2 3 4 5 6 7 8 Zucker SN, Fink EE, Bagati A, Mannava S, Bianchi-Smiraglia A, Bogner PN, Wawrzyniak JA, Foley C, Leonova KI, Grimm MJ, Moparthy K, Ionov Y, Wang J, Liu S, Sexton S, Kandel ES, Bakin AV, Zhang Y, Kaminski N, Segal BH, Nikiforov MA (2014). "Nrf2 amplifies oxidative stress via induction of Klf9". Mol. Cell. 53 (6): 916–28. doi:10.1016/j.molcel.2014.01.033. PMC   4049522 . PMID   24613345.
  8. ↑ Simmen FA, Su Y, Xiao R, Zeng Z, Simmen RC (2008). "The Krüppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression". Reprod. Biol. Endocrinol. 6: 41. doi: 10.1186/1477-7827-6-41 . PMC   2542371 . PMID   18783612.
  9. ↑ Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC (Jun 2003). "Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells". J. Biol. Chem. 278 (24): 21474–82. doi: 10.1074/jbc.M212098200 . PMID   12672823.

Further reading

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