KLF11 explained

Krueppel-like factor 11 is a protein that in humans is encoded by the KLF11 gene.^{[1] [2] [3]}

KLF11 is a mesoderm derived, zinc finger transcription factor in the Krüppel-like factor (KLF) family. It binds to SP1- like GC- rich sequences in epsilon and gamma globin gene promoters inhibiting cellular growth and causing apoptosis. In the regulation of genes, it is involved in cellular inflammation and differentiation, making it an essential factor in early embryonic development. This transcription factor binds to promoters of genes involved in cholesterol, prostaglandin, neurotransmitter, fat, and sugar metabolism, specifically pancreatic beta cell function. Defects in KLF11 affect glucose metabolism, insulin transcription, insulin processing, and insulin secretion which cause type 2 diabetes in adults and maturity-onset diabetes of the young type 7. These types of diabetes are caused by KLF11 interacting with co-repressors in the pancreatic islet beta cells. KLF11 has recently been shown to be involved in endometriosis since it regulated the expression of extracellular matrix genes. Its absence in extracellular matrix genes created a more fibrogenic response by the tissue. This was proved by creating a “knockout” model. The experiment showed that the absence of KLF11 showed higher amounts of fibrosis indicating that it prevents the growth of endometriotic lesions and inhibits pathological scarring.

^{[4] [5] [6]}

Interactions

KLF11 has been shown to interact with SIN3A.^{[7] [8]}

See also

• Krüppel-like factors
• Maturity onset diabetes of the young

Further reading

• Asano H, Li XS, Stamatoyannopoulos G . George Stamatoyannopoulos. FKLF, a novel Krüppel-like factor that activates human embryonic and fetal beta-like globin genes . Molecular and Cellular Biology . 19 . 5 . 3571–9 . May 1999 . 10207080 . 84149 . 10.1128/MCB.19.5.3571.
• Zhang JS, Moncrieffe MC, Kaczynski J, Ellenrieder V, Prendergast FG, Urrutia R . A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A . Molecular and Cellular Biology . 21 . 15 . 5041–9 . Aug 2001 . 11438660 . 87230 . 10.1128/MCB.21.15.5041-5049.2001 .
• Jia L, Young MF, Powell J, Yang L, Ho NC, Hotchkiss R, Robey PG, Francomano CA . Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis . Genomics . 79 . 1 . 7–17 . Jan 2002 . 11827452 . 10.1006/geno.2001.6683 .
• Ellenrieder V, Zhang JS, Kaczynski J, Urrutia R . Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor . The EMBO Journal . 21 . 10 . 2451–60 . May 2002 . 12006497 . 126002 . 10.1093/emboj/21.10.2451 .
• Ou XM, Chen K, Shih JC . Jean Chen Shih. Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene . The Journal of Biological Chemistry . 279 . 20 . 21021–8 . May 2004 . 15024015 . 10.1074/jbc.M312638200 . free .
• Ellenrieder V, Buck A, Harth A, Jungert K, Buchholz M, Adler G, Urrutia R, Gress TM . KLF11 mediates a critical mechanism in TGF-beta signaling that is inactivated by Erk-MAPK in pancreatic cancer cells . Gastroenterology . 127 . 2 . 607–20 . Aug 2004 . 15300592 . 10.1053/j.gastro.2004.05.018 . free .
• Cao S, Fernandez-Zapico ME, Jin D, Puri V, Cook TA, Lerman LO, Zhu XY, Urrutia R, Shah V . KLF11-mediated repression antagonizes Sp1/sterol-responsive element-binding protein-induced transcriptional activation of caveolin-1 in response to cholesterol signaling . The Journal of Biological Chemistry . 280 . 3 . 1901–10 . Jan 2005 . 15531587 . 10.1074/jbc.M407941200 . free .
• Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, Vaillant E, Benmezroua Y, Durand E, Bakaher N, Delannoy V, Vaxillaire M, Cook T, Dallinga-Thie GM, Jansen H, Charles MA, Clément K, Galan P, Hercberg S, Helbecque N, Charpentier G, Prentki M, Hansen T, Pedersen O, Urrutia R, Melloul D, Froguel P . Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function . Proceedings of the National Academy of Sciences of the United States of America . 102 . 13 . 4807–12 . Mar 2005 . 15774581 . 554843 . 10.1073/pnas.0409177102 . free .
• Huda Zoghbi . Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Buck A, Buchholz M, Wagner M, Adler G, Gress T, Ellenrieder V . The tumor suppressor KLF11 mediates a novel mechanism in transforming growth factor beta-induced growth inhibition that is inactivated in pancreatic cancer . Molecular Cancer Research . 4 . 11 . 861–72 . Nov 2006 . 17114344 . 10.1158/1541-7786.MCR-06-0081 . free .
• Florez JC, Saxena R, Winckler W, Burtt NP, Almgren P, Bengtsson Boström K, Tuomi T, Gaudet D, Ardlie KG, Daly MJ, Altshuler D, Hirschhorn JN, Groop L . The Krüppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people . Diabetes . 55 . 12 . 3620–4 . Dec 2006 . 17130512 . 10.2337/db06-0867 . free .
• Spittau B, Wang Z, Boinska D, Krieglstein K . Functional domains of the TGF-beta-inducible transcription factor Tieg3 and detection of two putative nuclear localization signals within the zinc finger DNA-binding domain . Journal of Cellular Biochemistry . 101 . 3 . 712–22 . Jun 2007 . 17252542 . 10.1002/jcb.21228 . 9730806 .
• Niu X, Perakakis N, Laubner K, Limbert C, Stahl T, Brendel MD, Bretzel RG, Seufert J, Päth G . Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells . Diabetologia . 50 . 7 . 1433–41 . Jul 2007 . 17479246 . 10.1007/s00125-007-0667-3 . free .

Notes and References

1. Cook T, Gebelein B, Mesa K, Mladek A, Urrutia R . Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth . The Journal of Biological Chemistry . 273 . 40 . 25929–36 . Oct 1998 . 9748269 . 10.1074/jbc.273.40.25929 . free .
2. Scohy S, Gabant P, Van Reeth T, Hertveldt V, Drèze PL, Van Vooren P, Rivière M, Szpirer J, Szpirer C . Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family . Genomics . 70 . 1 . 93–101 . Nov 2000 . 11087666 . 10.1006/geno.2000.6362 .
3. Web site: Entrez Gene: KLF11 Kruppel-like factor 11.
4. Daftary GS, Zheng Y, Tabbaa ZM, Schoolmeester JK, Gada RP, Grzenda AL, Mathison AJ, Keeney GL, Lomberk GA, Urrutia R . A novel role of the Sp/KLF transcription factor KLF11 in arresting progression of endometriosis . PLOS ONE . 8 . 3 . e60165 . 2013 . 23555910 . 3610699 . 10.1371/journal.pone.0060165 . 2013PLoSO...860165D . free .
5. Mathison A, Grzenda A, Lomberk G, Velez G, Buttar N, Tietz P, Hendrickson H, Liebl A, Xiong YY, Gores G, Fernandez-Zapico M, Larusso NF, Faubion W, Shah VH, Urrutia R . Role for Krüppel-like transcription factor 11 in mesenchymal cell function and fibrosis . PLOS ONE . 8 . 9 . e75311 . 2013 . 24069400 . 3775729 . 10.1371/journal.pone.0075311 . 2013PLoSO...875311M . free .
6. Spittau B, Krieglstein K . Klf10 and Klf11 as mediators of TGF-beta superfamily signaling . Cell and Tissue Research . 347 . 1 . 65–72 . 2012 . 21574058 . 10.1007/s00441-011-1186-6 . 14295737 .
7. Zhang JS, Moncrieffe MC, Kaczynski J, Ellenrieder V, Prendergast FG, Urrutia R . A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A . Molecular and Cellular Biology . 21 . 15 . 5041–9 . Aug 2001 . 11438660 . 87230 . 10.1128/MCB.21.15.5041-5049.2001 .
8. Ellenrieder V, Zhang JS, Kaczynski J, Urrutia R . Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2, an Sp1-like repressor . The EMBO Journal . 21 . 10 . 2451–60 . May 2002 . 12006497 . 126002 . 10.1093/emboj/21.10.2451 .