title: Shaking the family tree: identification of novel and biologically active alternatively spliced isoforms across the KLF family of transcription factors.
abstract: Alternative splicing represents a unique post-transcriptional mechanism that increases the complexity of the eukaryotic proteome-generating protein isoforms whose functions can be novel, diverse, and/or even antagonistic when compared to its full-length transcript. The KLF family of genes consists of ≥17 members, which are involved in the regulation of numerous critical cellular processes, including differentiation, cell proliferation, growth-related signal transduction, angiogenesis, and apoptosis. Using a strategy based on RT-PCR, selective cloning, and promoter-based assays of cancer-relevant genes, we identify and characterize the existence of multiple biologically active KLF splice forms across the entire family of proteins. We demonstrate biological function for a number of these isoforms. Furthermore, we highlight a possible functional interaction between full-length KLF4 and one of its splice variants in up-regulating cellular proliferation. Taken together, this report identifies for the first time a more complete view of the genomic and proteomic breadth and complexity of the KLF transcription factor family, revealing the existence of highly expressed and biologically active isoforms previously uncharacterized. In essence, knowing that these KLF isoforms exist provides the first step toward understanding the roles of these genes in human health and disease.
authors.affiliation: Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Camacho-Vanegas
authors.forename: Jacob
authors.initials: J
authors.lastname: Till
authors.forename: Irene
authors.initials: I
authors.lastname: Miranda-Lorenzo
authors.forename: Berrin
authors.initials: B
authors.lastname: Ozturk
authors.forename: Sandra Catalina
authors.initials: SC
authors.lastname: Camacho
authors.forename: John A
authors.initials: JA
authors.lastname: Martignetti
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D061986:MCF-7 Cells; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger; D011994:Recombinant Proteins