KLF9

Source: Wikipedia, the free encyclopedia.
KLF9
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_001206

NM_010638

RefSeq (protein)

NP_001197

NP_034768

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

Krueppel-like factor 9 is a

tumorigenesis.[8]

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000119138 - Ensembl, May 2017
  2. ^ a b c 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. PMID 1356762
    .
  6. ^ a b "Entrez Gene: KLF9 Kruppel-like factor 9".
  7. ^
    PMID 24613345
    .
  8. .
  9. .

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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