The biology of the mammalian Krüppel-like family of transcription factors

Abstract

Recent advances in molecular cloning have led to the identification of a large number of mammalian zinc finger-containing transcription factors that exhibit homology to the Drosophila melanogaster protein, Krüppel. Although the amino acid sequences in the zinc finger domains of these Krüppel-like factors (KLFs) are closely related to one another, the regions outside the zinc fingers of the proteins are usually unique. KLFs display seemingly different and broad biological properties with each functioning as an activator of transcription, a repressor or both. This review article provides a current phylogenetic classification of the identified KLFs to date. More importantly, the currently known biological activities of the KLFs in regulating transcription, cell proliferation, differentiation and development are summarized and compared. Further characterization of this interesting protein family should provide additional insights into the their respective regulatory role in various important biological processes.

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

“…Mouse KLF4 contains 483 amino acids, has a predicted molecular weight of 53 kD, and is 90% identical to human KLF4. The carboxyl terminus of KLF4 contains three C2H2-zinc fingers that are most closely related to another member of the family, KLF2 [4]. KLF4 is a nuclear protein whose cellular address depends on two nuclear localization signals [6].…”

“…A further subgroup of the C2H2-zinc finger proteins exhibits homology to the Drosophila melanogaster segmentation gene product, Krüppel [3]. Members of this subgroup are termed Krüppel-like factors (KLFs), and many KLFs exhibit tissue-selective expression and wide-ranging regulatory functions [4]. This review will focus on two members of the KLF family of transcription factors, Krüppel-like factor 4 (KLF4) and Krüppel-like factor 5 (KLF5), which are enriched in epithelial tissues but demonstrate contrasting biological activities.…”

KLF4, p21 and context-dependent opposing forces in cancer

“…A characteristic of this family of transcription factors is the three Krüppel-like zinc fingers. In humans, the KLF family comprises at least 25 members, which include both SP1-like and KLF-like factors [7][8][9][10][11][12] . These proteins share homologous DNA-binding domains and can interact with similar DNA sequences.…”

“…Some are expressed ubiquitously, such as SP1 and KLF6, whereas others are primarily expressed in certain tissues, such as intestinal KLF (IKLF, also known as KLF5) and gut-enriched KLF (GKLF, also known as KLF4). KLFs regulate the expression of a vast number of target genes that are involved in many cellular functions, ranging from differentiation to proliferation and apoptosis [7][8][9][10][11][12] .…”

TIEG-null mice display an osteopenic gender-specific phenotype

“…TIEG is expressed in numerous tissues [2][3][4][5][6][7] and is a member of the Krüppel-like family of transcription factors (KLF-10) which are known to be involved in antiproliferative and apoptotic inducing functions similar to those initiated by TGFβ action [8][9][10]. These factors bind to Sp-1-GC rich DNA elements via their zinc fingers and regulate the expression of genes involved in cell growth, differentiation and apoptosis [11][12][13].…”