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KLF5 : Kruppel-like factor 5 (intestinal)

Written2006-10Ceshi Chen, Yinfa Zhou, Jin-Tang Dong
The Center for Cell Biology, Cancer Research Albany Medical College MS355/350, Mail code 165, 47 New Scotland Ave. Albany, NY 12208, USA

(Note : for Links provided by Atlas : click)


Other aliasIKLF
LocusID (NCBI) 688
Atlas_Id 41074
Location 13q22.1  [Link to chromosome band 13q22]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
FBXL3 (13q22.3) / KLF5 (13q22.1)KLF5 (13q22.1) / TMC4 (19q13.42)RAP1GDS1 (4q23) / KLF5 (13q22.1)
Note FISH study in PC-3 prostate cancer cell line using BAC 505F3 as a probe


  Black box: Exon
Description KLF5 gene encompasses 4 exons which span about 18.7 kb of DNA. BAC clone RPCI-505F3 contains the complete KLF5 genome sequence.
Transcription about 3.4 Kb mRNA, 1374 bp open reading frame


  TAD: transactivation domain, PY: PPPSY sequence
Description 457 amino acids; about 55 kDa protein; KLF5 protein undergoes numerous post translational modifications: phosphorylation, acetylation, and ubiquitination. The major transactivation domain is proline rich and contains a PY motif (324-328), which can bind to E3 ubiquitin ligase WWP1. Three zinc finger domains at C-terminus can bind to GC rich DNA sequence.
Expression widely expressed in intestine, prostate, breast, lung, bladder, pancreas, placenta, uterus, skin, and skeletal muscle.
Localisation nucleus
Function KLF5 is a transcription factor. Many KLF5 target genes, such as PDGFa, PPARg, NFkB, cyclinD1, KLF4, and TCR, have been identified in different cell models. KLF5 regulates cell proliferation, cell cycle, apoptosis, and differentiation. KLF5 is an important transcription factor for cardiovascular remodeling and tumor angiogenesis. KLF5 is essential for mouse embryo development. Additionally, KLF5 may play an important role in several tumor types including breast, prostate, bladder, colon, esophagus, and skin.
Homology KLF5 gene is highly-conserved among species (from human to Drosophila). KLF5 belongs to the SP1/KLF transcription factor family


Somatic The KLF5 gene is rarely mutated in human prostate cancer. One point mutation (A --> G), which change Met294 to Val, has been found in the breast cancer cell line MDA-MB-231.

Implicated in

Entity Breast cancer
Disease The KLF5 gene is deleted in about 43% breast cancer cell lines. Consistently, KLF5 mRNA is down-regulated in these cell lines. In 9 breast cancer cell lines without KLF5 mRNA loss, KLF5 protein is excessively degraded through ubiquitin-proteasome pathway. Forced expression of KLF5 inhibits T-47D cancer cell growth in vitro. In contrast, KLF5 expression is upregulated in clinical breast tumor samples (see below)
Prognosis Recently, high level of KLF5 mRNA expression is found to be associated with shorter survival for breast cancer patients. Using tissue microarray, we performed immunohistochemical staining with the anti-KLF5 Ab. The results suggest that KLF5 protein is generally weak in normal breast epithelial cells but strongly positive in breast tumors. Therefore, KLF5 expression is probably a good prognosis marker for breast cancer.
Entity Prostate cancer
Disease The KLF5 gene is deleted in about 33% prostate cancer cell lines/xenografts. Consistently, KLF5 mRNA is down-regulated in these samples compared to three immortalized prostate epithelial cell lines. In PC-3 prostate cancer cell line in which KLF5 mRNA is at normal high level, KLF5 protein is excessively degraded by over-expression of WWP1. KLF5 protein is highly expressed in normal prostate epithelial cells (Figure 5). Forced expression of KLF5 inhibits DU145 and 22Rv1 prostate cancer cell growth in vitro. In contrast, KLF5 knock-down decreases RWPE1 immortalized prostate epithelial cell growth in vitro. These results suggest that KLF5 may play a context dependent role in prostate cancer.
Entity Bladder cancer
Disease KLF5 mRNA is down-regulated in several bladder cancer cell lines. In TSu-Pr1 cell line, KLF5 over-expression promotes tumorigenesis in SCID mice. Consistently, KLF5 promotes cell cycle progression from G1 to S phase. Interestingly, KLF5 appears to promote tumor angiogenesis. Microarray analysis identified a number of angiogenic factors that are potentially regulated by KLF5, including HBP17, TGFa, and PDGFa. These findings suggest that the KLF5 transcription factor may play an oncogenic role in bladder cancer.
Entity Intestinal and colon cancer
Disease Down-regulation of KLF5 may be an early event in intestinal tumorigenesis. Expression of KLF5 in non-transformed intestinal epithelial cells enhances cell growth; however, KLF5 inhibits cell growth in colon cancer cell lines. Another group found that all-trans retinoic acid inhibits intestinal epithelial cell growth in vitro through inhibiting KLF5 expression. At the same time, lipopolysaccharide (LPS) induces proinflammatory response in intestinal epithelial cells through inducing KLF5 expression. These findings suggest that KLF5 may play an important but yet to be identified role in intestinal and colon cancer.
Entity Esophagus cancer
Disease KLF5 is expressed in proliferating cells of the gastrointestinal tract, including the esophagus. Expression of KLF5 in a poorly differentiated esophageal squamous cancer cell line TE2 inhibits proliferation and invasion, decreases viability after treatment with hydrogen peroxide and UV irradiation, and increases anoikis. KLF5 upregulates the cdk inhibitor p21(waf1/cip1) and pro-apoptotic protein BAX following UV irradiation.
Entity Skin cancer
Disease KLF5 is expressed predominantly in the basal layers of the developing epidermis, in the basal layers of cells of the inner root sheath, and in matrix cells of adult human hair follicles. In a transgenic mouse model, KLF5 over-expression in the basal layers of the epidermis causes abnormal epidermal development and differentiation. KLF5 over-expression may decrease the proliferation of stem cell populations of bulge keratinocytes.
Entity Cardiovascular remodeling
Disease KLF5 hemizygous knock-out mice reduce cardiac hypertrophy and interstitial fibrosis upon infusion of angiotensin II. Additionally, KLF5 may play a role in antherosclerosis and restenosis through regulating vascular smooth muscle cells.


Regulation of platelet-derived growth factor-A chain by Kruppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB.
Aizawa, K., Suzuki, T., Kada, N., Ishihara, A., Kawai-Kowase, K., Matsumura, T., Sasaki, K., Munemasa, Y., Manabe, I., Kurabayashi, M., Collins, T., and Nagai, R.
J Biol Chem 2004; 279: 70-76.
PMID 14573617
Intestinal tumor progression is associated with altered function of KLF5.
Bateman, N. W., Tan, D., Pestell, R. G., Black, J. D., and Black, A. R.
J Biol Chem 2004; 279: 12093-12101.
PMID 14726538
Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells.
Chanchevalap, S., Nandan, M. O., McConnell, B. B., Charrier, L., Merlin, D., Katz, J. P., and Yang, V. W.
Nucleic Acids Res 2006; 34: 1216-1223.
PMID 16500892
KLF5 promotes cell proliferation and tumorigenesis through gene regulationin the TSU-Pr1 human bladder cancer cell line.
Chen, C., Benjamin, M. S., Sun, X., Otto, K. B., Guo, P., Dong, X. Y., Bao, Y., Zhou, Z., Cheng, X., Simons, J. W., and Dong, J. T.
Int J Cancer 2006; 118: 1346-1355.
PMID 16184550
KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer.
Chen, C., Bhalala, H. V., Vessella, R. L., and Dong, J. T.
Prostate 2003; 55: 81-88.
PMID 12661032
Ubiquitin-proteasome degradation of KLF5 transcription factor in cancer and untransformed epithelial cells.
Chen, C., Sun, X., Ran, Q., Wilkinson, K. D., Murphy, T. J., Simons, J. W., and Dong, J. T.
Oncogene 2005; 24: 3319-3327.
PMID 15735697
Opposing effects of Kruppel-like factor 4 (gut-enriched Kruppel-like factor) and Kruppel-like factor 5 (intestinal-enriched Kruppel-like factor) on the promoter of the Kruppel-like factor 4 gene.
Dang, D. T., Zhao, W., Mahatan, C. S., Geiman, D. E., and Yang, V. W;
Nucleic Acids Res 2002; 30: 2736-2741.
PMID 12087155
The deacetylase HDAC1 negatively regulates the cardiovascular transcription factor Kruppel-like factor 5 through direct interaction.
Matsumura, T., Suzuki, T., Aizawa, K., Munemasa, Y., Muto, S., Horikoshi, M., and Nagai, R.
J Biol Chem 2005; 280: 12123-12129.
PMID 15668237
Positive and negative regulation of the cardiovascular transcription factor KLF5 by p300 and the oncogenic regulator SET through interaction and acetylation on the DNA-binding domain.
Miyamoto, S., Suzuki, T., Muto, S., Aizawa, K., Kimura, A., Mizuno, Y., Nagino, T., Imai, Y., Adachi, N., Horikoshi, M., and Nagai, R.
Mol Cell Biol 2003; 23: 8528-8541.
PMID 14612398
Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4, but not KLF5, in bladder cancer.
Ohnishi, S., Ohnami, S., Laub, F., Aoki, K., Suzuki, K., Kanai, Y., Haga, K., Asaka, M., Ramirez, F., and Yoshida, T.
Biochem Biophys Res Commun 2003; 308: 251-256.
PMID 12901861
Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation.
Oishi, Y., Manabe, I., Tobe, K., Tsushima, K., Shindo, T., Fujiu, K., Nishimura, G., Maemura, K., Yamauchi, T., Kubota, N., Suzuki, R., Kitamura, T., Akira, S., Kadowaki, T., and Nagai, R.
Cell Metab 2005; 1: 27-39.
PMID 16054042
Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling.
Shindo, T., Manabe, I., Fukushima, Y., Tobe, K., Aizawa, K., Miyamoto, S., Kawai-Kowase, K., Moriyama, N., Imai, Y., Kawakami, H., Nishimatsu, H., Ishikawa, T., Suzuki, T., Morita, H., Maemura, K., Sata, M., Hirata, Y., Komukai, M., Kagechika, H., Kadowaki, T., Kurabayashi, M., and Nagai, R.
Nat Med 2002; 8: 856-863.
PMID 12101409
Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis.
Sur, I., Rozell, B., Jaks, V., Bergstrom, A., and Toftgard, R.
J Cell Sci 2006; 119: 3593-3601.
PMID 16912082
Human Kruppel-like factor5/KLF5: synergy with NF-kappaB/Rel factors and expression in human skin and hair follicles.
Sur, I., Unden, A. B., and Toftgard, R.
Eur J Cell Biol 2002; 81: 323-334.
PMID 12113473
Regulation of T-cell receptor D beta 1 promoter by KLF5 through reiterated GC-rich motifs.
Yang, X. O., Doty, R. T., Hicks, J. S., and Willerford, D. M.
Blood 2003; 101: 4492-4499.
PMID 12576331
KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells.
Yang, Y., Goldstein, B. G., Chao, H. H., and Katz, J. P.
Cancer Biol Ther 2005; 4: 1216-1221.
PMID 16357509
Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function.
Zhang, Z. and Teng, C. T.
Nucleic Acids Res 2003; 31: 2196-2208.
PMID 12682370


This paper should be referenced as such :
Dong, JT ; Zhou, Y ; Chen, C
KLF5 (Kruppel-like factor 5 (intestinal))
Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):19-22.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  FBXL3/KLF5 (13q22)

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)688
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
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indexed on : Thu Oct 18 17:40:48 CEST 2018

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