title: Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization.
abstract: Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis) are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis.
authors: Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
authors: Trianna W
authors: TW
authors: Utami
authors: Keiko
authors: K
authors: Miyoshi
authors: Hiroko
authors: H
authors: Hagita
authors: Ryna Dwi
authors: RD
authors: Yanuaryska
authors: Taigo
authors: T
authors: Horiguchi
authors: Takafumi
authors: T
authors: Noma
mesh_terms: D000565:Ameloblasts; D000566:Amelogenesis / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D003746:Dental Enamel Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C514056:Amtn protein, rat; D003746:Dental Enamel Proteins; D051741:Kruppel-Like Transcription Factors; D007976:Leupeptins; D034741:RNA, Small Interfering; C529065:Sp6 protein, rat; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde