Molecular Analysis of Kruppel, a Segmentation Gene of Drosophila melanogaster

Jäckle, Herbert; Rosenberg, Urs B.; Preiss, Anette; Seifert, E; Knipple, Douglas C.; Kienlin, Andrea; Lehmann, Robert

doi:10.1101/sqb.1985.050.01.058

Cited by 25 publications

(10 citation statements)

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“…This family of proteins shares homology with the founding member, Krü ppel, which was first identified in Drosophila melanogaster by deletion of a gene that causes a ''crippled'' phenotype. (1)(2)(3) Phylogenetic analysis indicates that the KLF proteins are closely related to the Sp1 and Krox zinc finger protein families, but the KLF family is distinct in that the proteins contain three highly conserved zinc fingers with additional conserved residues between each finger. (4)(5)(6)(7) KLFs recognize and bind to very similar ''GT-box'' or ''CACCC element'' consensus sequences; thus, the specificity of their activities is determined by differing amino termini and/or by tissue-specific expression.…”

Section: Introductionmentioning

confidence: 99%

The diverse functions of Krüppel‐like factors 4 and 5 in epithelial biology and pathobiology

et al. 2007

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The Krüppel-like factors (KLFs) comprise a family of evolutionarily conserved zinc finger transcription factors that regulate numerous biological processes including proliferation, differentiation, development and apoptosis. KLF4 and KLF5 are two closely related members of this family and are both highly expressed in epithelial tissues. In the intestinal epithelium, KLF4 is expressed in terminally differentiated epithelial cells at the villus borders of the mucosa and inhibits cell growth, while KLF5 is expressed in proliferating epithelial cells at the base of the intestinal crypts and promotes cell growth. KLF4 and KLF5 respond to a myriad of external stress stimuli and are likely involved in restoring cellular homeostasis following exposure to stressors. Confirming their importance in maintaining tissue integrity, KLF4 and KLF5 are both dysregulated in various types of cancer. Here we review the recent advances in defining the physiological and pathobiological roles of KLF4 and KLF5, focusing on their functions in the intestinal epithelium.

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Section: Introductionmentioning

confidence: 99%

The diverse functions of Krüppel‐like factors 4 and 5 in epithelial biology and pathobiology

et al. 2007

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“…[15][16][17] The first mammalian Krüppel, erythroid Krüppel-like factor (EKLF/KLF1), was identified in red blood cells. 18 This factor was subsequently found to play an important role in ␤-globin gene synthesis and erythrocyte development.…”

Section: The Krü Ppel-like Factor Family Of Transcription Factorsmentioning

confidence: 99%

Role of Krüppel-Like Transcription Factors in Endothelial Biology

Atkins

Jain

2007

Circulation Research

372

317

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“…[1][2][3][4] Thus, the German researchers named this gene Krüppel (English "cripple"). A conserved family of nuclear proteins encoded by Drosophila Krüppel were identified in 1986 and exhibited a striking structural similarity to the DNA-binding "finger motif " of transcription factor IIIA.…”

Section: Introductionmentioning

confidence: 99%

Role of Krüppel-like factors in leukocyte development, function, and disease

Cao

Sun

Icli

et al. 2010

Blood

151

120

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IntroductionLeukocyte development requires the coordination of stage-specific transcription factors to help orchestrate the processes by which a progenitor cell emerges as a functional leukocyte. Indeed, aberrant expression or function of many of these transcription factors has been associated with several disease conditions, such as leukemia, lymphoma, autoimmunity, and chronic inflammation. Moreover, recent studies have indicated that Krüppel-like factors (KLFs) may be among those key trans-acting factors contributing to the orchestration of several aspects of leukocyte biology, including cell lineage commitment, differentiation, and function.The original Krüppel factor was characterized in Drosophila melanogaster as a "gap" segmentation gene, homozygous mutation of which resulted in the absence of thorax and anterior abdomen in embryos. [1][2][3][4] Thus, the German researchers named this gene Krüppel (English "cripple"). A conserved family of nuclear proteins encoded by Drosophila Krüppel were identified in 1986 and exhibited a striking structural similarity to the DNA-binding "finger motif " of transcription factor IIIA. 5 The first mammalian gene with homology to Krüppel was identified in 1993, and its encoded protein was named erythroid Krüppel-like factor (EKLF) in accordance with its erythroid cell-specific expression. 6 The function of EKLF was demonstrated by the fact that EKLF bound to human and murine adult ␤-globin CACCC elements via its DNA-binding domain, whereas the non-DNA-binding domain mediated transcriptional activation. 7 The importance of EKLF in differentiation and development was later demonstrated by loss-offunction studies showing that homozygous EKLF Ϫ/Ϫ mice developed a fatal ␤-thalassemia during fetal liver erythropoiesis. 8,9 To date, members of the mammalian KLF family number 17. 10 Identified by various experimental approaches, KLF1 (EKLF) through KLF17 have been termed according to their chronologic order of identification ( Figure 1). Each family member is a zinc finger transcription factor. The distinguishing feature of KLFs compared with other zinc finger-containing proteins, therefore, is the presence of a highly conserved DNA-binding domain composed of 3 C 2 H 2 zinc fingers at or near the C-terminus. [11][12][13] As such, most KLFs are able to bind the CACCC element and GC box consensus sequences. Furthermore, the KLFs share a highly conserved 7-residue sequence, TGEKP(Y/F)X, between zinc fingers. 14 The non-DNA-binding regions of each, however, are highly divergent and can function as trans-activation or trans-repression domains. Collectively, these features distinguish the KLFs from the larger family of zinc-finger transcription factors ( Figure 1A).By regulating gene transcription, KLFs are involved in many physiologic and pathologic processes, such as cell differentiation, proliferation, cell growth, and apoptosis during normal development or under different disease conditions ( Figure 1B). 13,15,16 This review focuses on the transcriptional control of leukocyte cell b...

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Molecular Analysis of Kruppel, a Segmentation Gene of Drosophila melanogaster

Cited by 25 publications

References 1 publication

The diverse functions of Krüppel‐like factors 4 and 5 in epithelial biology and pathobiology

The diverse functions of Krüppel‐like factors 4 and 5 in epithelial biology and pathobiology

Role of Krüppel-Like Transcription Factors in Endothelial Biology

Role of Krüppel-like factors in leukocyte development, function, and disease

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