Molecules in focusKrüppel-like transcription factors: A functional family
Introduction
Krüppel-like factors (Klfs) are named after the Drosophila embryonic pattern regulator Krüppel, with which their DNA-binding domains show homology. They are transcriptional regulators implicated in a broad range of cellular processes (Dang, Pevsner, & Yang, 2000). The first mammalian Klf gene, Klf1 or Erythroid Krüppel-like factor (Eklf), was cloned in 1993. To date, 17 members of the Klf family have been identified in mammalian cells and according to recent nomenclature are referred to as Klf1–Klf17 (Suske, Bruford, & Philipsen, 2005).
Section snippets
Structure
The distinguishing feature of the Klf family is the presence of three highly conserved classical Cys2/His2 zinc fingers (Fig. 1). Zinc fingers 1 and 2 contain 23 residues, while the third finger has only 21 residues. These fingers are located at the carboxyl terminus of the protein and enable Klfs to bind to related GC- and CACCC-boxes of DNA (Kaczynski, Cook, & Urrutia, 2003; Suske et al., 2005). The fingers are connected by the characteristic Krüppel-link, a seven-amino acid spacer
Expression, activation and competition within the family
Certain Klfs show a tissue restricted expression pattern, but most are widely expressed (Table 1). The mechanisms regulating expression of Klfs are incompletely defined, although it is becoming clear that they are often differentially expressed during differentiation. Klf2 is downregulated upon activation of T cells. Similarly Klf4 shows changes in expression during B-cell development and activation. Klfs are also expressed in response to physiological stresses. For example Klf5 plays a major
Biological function
There has been considerable progress in defining the physiological functions of several Klfs, principally by the generation of knockout mice, as detailed below and summarised in Table 1.
Possible medical applications
A number of Klfs, most notably Klf1 and Klf2, have been implicated in the regulation of globin gene expression and are therefore of interest in the study of conditions such as thalassemia and sickle cell anemia. In addition, deregulation of Klf expression is a cause or contributory factor in a wide variety of cancers, which reflects the fundamental role of Klfs in the regulation of cell proliferation and death. For example Klf4 is a tumour suppressor gene, silenced in a number of
References (20)
- et al.
The biology of the mammalian Kruppel-like family of transcription factors
Int. J. Biochem. Cell Biol.
(2000) - et al.
Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6
Blood
(2006) - et al.
Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation
Cell Metab.
(2005) - et al.
Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Kruppel-like factor 9/basic transcription element-binding protein-1 (Bteb1) gene
J. Biol. Chem.
(2004) - et al.
Functional study of transcription factor KLF11 by targeted gene inactivation
Blood Cells Mol. Dis.
(2005) - et al.
Mammalian SP/KLF transcription factors: Bring in the family
Genomics
(2005) - et al.
The transcription factor KLF11 can induce gamma-globin gene expression in the setting of in vivo adult erythropoiesis
J. Cell Biochem.
(2007) - et al.
Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy
Proc. Natl. Acad. Sci. U.S.A.
(2007) - et al.
Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells
Mol. Cell Biol.
(2007) - et al.
Sp1- and Kruppel-like transcription factors
Genome Biol.
(2003)
Cited by (326)
Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation
2024, Biochimica et Biophysica Acta - Gene Regulatory MechanismsCharacterizing the SREB G protein-coupled receptor family in fish: Brain gene expression and genomic differences in upstream transcription factor binding sites
2023, Comparative Biochemistry and Physiology -Part A : Molecular and Integrative PhysiologyAnalysis of KLF7 and KLF5 transcription factors gene variants in coronary artery disease
2023, Revista Portuguesa de CardiologiaGenome-wide survey identifies TNNI2 as a target of KLF7 that inhibits chicken adipogenesis via downregulating FABP4
2023, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms