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.

Fig. 1

Classification of related human Krüppel-like factors. Human KLF1 and related proteins were identified by BLAST searching, then multiple aligned using the PileUp program of GCG (Genetics Computer Group version 9.0, Madison, WI). The relationship of 18 Krüppel-like proteins was visualized as an unrooted phylogram using a heuristic search with Phylogeny Analysis Using Parsimony (PAUP version 4.0b3a; Sinauer Associates, Sunderland, MA). The horizontal bar in the left lower corner of the figure indicates 100 amino acid changes. Branch lengths are proportional to amino acid changes. For keys to abbreviations, see Table 1. RFLAT-1 and KKLF have not received a HNGC nomenclature. RFLAT-1 is RANTES (regulated upon activation, normal T cells expressed and secreted) factor of late activated T lymphocytes-1 [117]. Its gene is expressed in T cells 3 days after activation and coincides with RANTES expression. KKLF represents kidney-enriched Krüppel-like factor whose identification was only recently described [118]. It functions to repress transcription of two kidney-specific chloride channel genes by blocking the activating effect of another transcription factor, MA2 [118].