title: Katanin-p80 gene promoter characterization and regulation via Elk1.
abstract: Katanin is an ATPase family member protein that participates in microtubule severing. It has heterodimeric structure consisting of 60 kDa (katanin-p60) and 80 kDa (katanin-p80) subunits encoded by KATNA1 and KATNB1 genes, respectively. Katanin-p60 has the enzymatic activity for microtubule severing, whereas katanin-p80 consists of multiple domains with different functions such as targeting katanin-p60 to the centrosome, augmenting microtubule severing by katanin-p60, and even suppressing microtubule severing. Despite the various important functions of katanin-p80, its transcriptional regulation has not been studied yet. Elk1 transcription factor has been shown to interact with microtubules and regulate the transcription of another microtubule severing protein, spastin. In spite of katanin's importance, and structural and functional similarities to spastin, there is no study on the transcriptional regulation of katanin yet. In this study, we aimed to characterize KATNB1 promoter and analyze the effects of Elk1 on katanin-p80 expression. We identified a 518- bp TATA-less promoter including a critical CpG island and GC boxes as an optimal promoter, and sequential deletion of CpG island and the GC elements gradually decreased the KATNB1 promoter activity. In addition, we showed Elk1 binding on the KATNB1 promoter by EMSA. We found that Elk1 activated KATNB1 promoter, and increased both mRNA and protein levels of katanin-p80 in SH-SY5Y cells. On the other hand, KCl treatment increasing SUMOylation decreased KATNB1 promoter activity. Since microtubule severing is an important cellular mechanism of which malfunctions result in serious diseases such as spastic paraplegia, Alzheimer's disease and cell cycle related disorders, identification of KATNB1 transcriptional regulation is crucial in understanding the coordination of microtubule severing activity by different proteins in the cells.
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Selçuk
authors.forename: Koray
authors.initials: K
authors.lastname: Kırımtay
authors.forename: Derya
authors.initials: D
authors.lastname: Canbaz
authors.forename: Güher Işık
authors.initials: GI
authors.lastname: Cesur
authors.forename: Sirin
authors.initials: S
authors.lastname: Korulu
authors.forename: Arzu
authors.initials: A
authors.lastname: Karabay
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019295:Computational Biology; D018899:CpG Islands / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D000074201:Katanin; D008870:Microtubules / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology; D058207:Sumoylation / Q000187:drug effects; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494112:ELK1 protein, human; D050807:ets-Domain Protein Elk-1; D012965:Sodium Chloride; D000251:Adenosine Triphosphatases; D000074201:Katanin
references.citation: Mol Cell Neurosci. 2009 Jan;40(1):111-9
references.pmid: 19013529
references.citation: PLoS Biol. 2004 Dec;2(12):e429
references.pmid: 15562320
references.citation: Biochem Biophys Res Commun. 2009 Dec 18;390(3):872-6
references.pmid: 19840774
references.citation: Mol Endocrinol. 2011 Sep;25(9):1539-49
references.pmid: 21757506
references.citation: Cell. 1998 Apr 17;93(2):277-87
references.pmid: 9568719
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3651-3
references.pmid: 12824386
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Curr Pharm Des. 2011;17(31):3413-7
references.pmid: 21902667
references.citation: Mol Cell. 2003 Jul;12(1):63-74
references.pmid: 12887893
references.citation: Cell. 1993 Nov 5;75(3):419-29
references.pmid: 8221885
references.citation: Oncogene. 2000 Dec 18;19(55):6503-13
references.pmid: 11175366
references.citation: Mol Cell Biol. 2001 Apr;21(8):2802-14
references.pmid: 11283259
references.citation: Nat Genet. 1999 Nov;23(3):296-303
references.pmid: 10610178
references.citation: J Cell Sci. 2000 May;113 ( Pt 9):1623-33
references.pmid: 10751153
references.citation: J Biol Chem. 2004 Jun 25;279(26):27233-8
references.pmid: 15123604
references.citation: Brain Res Mol Brain Res. 2003 May 12;113(1-2):57-66
references.pmid: 12750007
references.citation: Mol Cell. 2004 Feb 27;13(4):611-7
references.pmid: 14992729
references.citation: J Cell Biol. 1999 Apr 19;145(2):305-15
references.pmid: 10209026
references.citation: Nat Rev Genet. 2007 Jun;8(6):424-36
references.pmid: 17486122
references.citation: Bioinformatics. 2002 Feb;18(2):333-4
references.pmid: 11847087
references.citation: J Cell Physiol. 2002 Jun;191(3):257-68
references.pmid: 12012321
references.citation: J Neurosci. 1998 Jan 1;18(1):214-26
references.pmid: 9412502
references.citation: J Biol Chem. 2002 Feb 8;277(6):4455-64
references.pmid: 11724806
references.citation: Gene. 2004 Jan 7;324:1-14
references.pmid: 14693367
references.citation: PLoS One. 2012;7(5):e36505
references.pmid: 22574173
references.citation: Neuropathol Appl Neurobiol. 2013 Jun;39(4):320-34
references.pmid: 23289367
references.citation: J Neurosci. 2011 Mar 2;31(9):3309-19
references.pmid: 21368042
references.citation: ASN Neuro. 2011 Nov 03;3(4):
references.pmid: 21973168
references.citation: J Neurosci. 2005 Jun 8;25(23):5573-83
references.pmid: 15944385
references.citation: Genome Biol. 2010;11(3):R29
references.pmid: 20222956
references.citation: J Neurochem. 2011 May;117(4):724-34
references.pmid: 21395583
references.citation: BMC Biol. 2008 Jul 09;6:31
references.pmid: 18613979
references.citation: Cell. 2004 Jun 25;117(7):859-72
references.pmid: 15210108
references.citation: Mol Biol Cell. 2008 Apr;19(4):1485-98
references.pmid: 18234839
references.citation: Cytotechnology. 2006 Nov;52(3):159-70
references.pmid: 19002874