KLF6 explained

Krueppel-like factor 6 is a protein that in humans is encoded by the KLF6 gene.^[1]

It is a tumor suppressor gene.^[2]

Function

This gene encodes a nuclear protein that has three zinc fingers at the end of its C-terminal domain, a serine/threonine-rich central region, and an acidic domain lying within the N-terminal region. The zinc fingers of this protein are responsible for the specific DNA binding with the guanine-rich core promoter elements. The central region might be involved in activation or posttranslational regulatory pathways, and the acidic N-terminal domain might play an important role in the process of transcriptional activation. It is capable of activating transcription approximately 4-fold either on homologous or heterologous promoters. The DNA binding and transcriptional activity of this protein, in conjunction with its expression pattern, suggests that this protein may participate in the regulation and/or maintenance of the basal expression of pregnancy-specific glycoprotein genes and possibly other TATA box-less genes. Two transcript variants encoding the same protein have been found for this gene.^[3]

Interactions

KLF6 has been shown to interact with Sp1 transcription factor.^[4]

See also

• Kruppel-like factors

Further reading

• Narla G, Friedman SL, Martignetti JA . Krüppel cripples prostate cancer: KLF6 progress and prospects . The American Journal of Pathology . 162 . 4 . 1047–52 . Apr 2003 . 12651597 . 1851219 . 10.1016/S0002-9440(10)63901-6 .
• El Rouby S, Newcomb EW . Identification of Bcd, a novel proto-oncogene expressed in B-cells . Oncogene . 13 . 12 . 2623–30 . Dec 1996 . 9000136 .
• Koritschoner NP, Bocco JL, Panzetta-Dutari GM, Dumur CI, Flury A, Patrito LC . A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene . The Journal of Biological Chemistry . 272 . 14 . 9573–80 . Apr 1997 . 9083102 . 10.1074/jbc.272.14.9573 . free.
• Suzuki T, Yamamoto T, Kurabayashi M, Nagai R, Yazaki Y, Horikoshi M . Isolation and initial characterization of GBF, a novel DNA-binding zinc finger protein that binds to the GC-rich binding sites of the HIV-1 promoter . Journal of Biochemistry . 124 . 2 . 389–95 . Aug 1998 . 9685731 . 10.1093/oxfordjournals.jbchem.a022124 .
• Ratziu V, Lalazar A, Wong L, Dang Q, Collins C, Shaulian E, Jensen S, Friedman SL . Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis . Proceedings of the National Academy of Sciences of the United States of America . 95 . 16 . 9500–5 . Aug 1998 . 9689109 . 21367 . 10.1073/pnas.95.16.9500 . 1998PNAS...95.9500R . free .
• Okano J, Opitz OG, Nakagawa H, Jenkins TD, Friedman SL, Rustgi AK . The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact . FEBS Letters . 473 . 1 . 95–100 . May 2000 . 10802067 . 10.1016/S0014-5793(00)01468-X . 34923598 .
• Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM, Ferrari AC, Martignetti JA, Friedman SL . KLF6, a candidate tumor suppressor gene mutated in prostate cancer . Science . 294 . 5551 . 2563–6 . Dec 2001 . 11752579 . 10.1126/science.1066326 . 2001Sci...294.2563N . 31619019 .
• Botella LM, Sánchez-Elsner T, Sanz-Rodriguez F, Kojima S, Shimada J, Guerrero-Esteo M, Cooreman MP, Ratziu V, Langa C, Vary CP, Ramirez JR, Friedman S, Bernabéu C . Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury . Blood . 100 . 12 . 4001–10 . Dec 2002 . 12433697 . 10.1182/blood.V100.12.4001 . free .
• Chen HK, Liu XQ, Lin J, Chen TY, Feng QS, Zeng YX . [Mutation analysis of KLF6 gene in human nasopharyngeal carcinomas] . AI Zheng = Aizheng = Chinese Journal of Cancer . 21 . 10 . 1047–50 . Oct 2002 . 12508640 .
• Warke VG, Nambiar MP, Krishnan S, Tenbrock K, Geller DA, Koritschoner NP, Atkins JL, Farber DL, Tsokos GC . Transcriptional activation of the human inducible nitric-oxide synthase promoter by Kruppel-like factor 6 . The Journal of Biological Chemistry . 278 . 17 . 14812–9 . Apr 2003 . 12590140 . 10.1074/jbc.M300787200 . free .
• Chen C, Hyytinen ER, Sun X, Helin HJ, Koivisto PA, Frierson HF, Vessella RL, Dong JT . Deletion, mutation, and loss of expression of KLF6 in human prostate cancer . The American Journal of Pathology . 162 . 4 . 1349–54 . Apr 2003 . 12651626 . 1851229 . 10.1016/S0002-9440(10)63930-2 .
• Jeng YM, Hsu HC . KLF6, a putative tumor suppressor gene, is mutated in astrocytic gliomas . International Journal of Cancer . 105 . 5 . 625–9 . Jul 2003 . 12740910 . 10.1002/ijc.11123 . 25600692 .
• Bayat A, Watson JS, Stanley JK, Ferguson MW, Ollier WE . Genetic susceptibility to dupuytren disease: association of Zf9 transcription factor gene . Plastic and Reconstructive Surgery . 111 . 7 . 2133–9 . Jun 2003 . 12794452 . 10.1097/01.PRS.0000060531.98180.32 . 22210744 .
• Reeves HL, Narla G, Ogunbiyi O, Haq AI, Katz A, Benzeno S, Hod E, Harpaz N, Goldberg S, Tal-Kremer S, Eng FJ, Arthur MJ, Martignetti JA, Friedman SL . Kruppel-like factor 6 (KLF6) is a tumor-suppressor gene frequently inactivated in colorectal cancer . Gastroenterology . 126 . 4 . 1090–103 . Apr 2004 . 15057748 . 10.1053/j.gastro.2004.01.005 . free .
• Kimmelman AC, Qiao RF, Narla G, Banno A, Lau N, Bos PD, Nuñez Rodriguez N, Liang BC, Guha A, Martignetti JA, Friedman SL, Chan AM . Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6 . Oncogene . 23 . 29 . 5077–83 . Jun 2004 . 15064720 . 10.1038/sj.onc.1207662 . free .
• Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL . Gene expression profiling predicts clinical outcome of prostate cancer . The Journal of Clinical Investigation . 113 . 6 . 913–23 . Mar 2004 . 15067324 . 362118 . 10.1172/JCI20032 .
• Rubinstein M, Idelman G, Plymate SR, Narla G, Friedman SL, Werner H . Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: potential interactions between KLF6 and p53 . Endocrinology . 145 . 8 . 3769–77 . Aug 2004 . 15131018 . 10.1210/en.2004-0173 . free .

Notes and References

1. Onyango P, Koritschoner NP, Patrito LC, Zenke M, Weith A . Assignment of the gene encoding the core promoter element binding protein (COPEB) to human chromosome 10p15 by somatic hybrid analysis and fluorescence in situ hybridization . Genomics . 48 . 1 . 143–4 . Feb 1998 . 9503030 . 10.1006/geno.1997.5124 .
2. Li D, Yea S, Dolios G, Martignetti JA, Narla G, Wang R, Walsh MJ, Friedman SL . Regulation of Kruppel-like factor 6 tumor suppressor activity by acetylation . Cancer Research . 65 . 20 . 9216–25 . Oct 2005 . 16230382 . 10.1158/0008-5472.CAN-05-1040 .
3. Web site: Entrez Gene: KLF6 Kruppel-like factor 6.
4. Botella LM, Sánchez-Elsner T, Sanz-Rodriguez F, Kojima S, Shimada J, Guerrero-Esteo M, Cooreman MP, Ratziu V, Langa C, Vary CP, Ramirez JR, Friedman S, Bernabéu C . Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury . Blood . 100 . 12 . 4001–10 . Dec 2002 . 12433697 . 10.1182/blood.V100.12.4001 . free .