Gutenberg Open Science: Non-secreted clusterin isoforms are translated in rare amounts from distinct human mRNA variants and do not affect bax-mediated apoptosis or the NF-kappaB signaling pathway

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7419

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DC Field	Value	Language
dc.contributor.author	Prochnow, Hans	-
dc.contributor.author	Gollan, Rene	-
dc.contributor.author	Rohne, Philipp	-
dc.contributor.author	Hassemer, Matthias	-
dc.contributor.author	Koch-Brandt, Claudia	-
dc.contributor.author	Baiersdörfer, Markus	-
dc.date.accessioned	2022-07-14T08:28:09Z	-
dc.date.available	2022-07-14T08:28:09Z	-
dc.date.issued	2013	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7433	-
dc.description.abstract	Clusterin, also known as apolipoprotein J, is expressed from a variety of tissues and implicated in pathological disorders such as neurodegenerative diseases, ischemia and cancer. In contrast to secretory clusterin (sCLU), which acts as an extracellular chaperone, the synthesis, subcellular localization and function(s) of intracellular CLU isoforms is currently a matter of intense discussion. By investigating human CLU mRNAs we here unravel mechanisms leading to the synthesis of distinct CLU protein isoforms and analyze their subcellular localization and their impact on apoptosis and on NF-kappaB-activity. Quantitative PCR-analyses revealed the expression of four different stress-inducible CLU mRNA variants in non-cancer and cancer cell lines. In all cell lines variant 1 represents the most abundant mRNA, whereas all other variants collectively account for no more than 0.34% of total CLU mRNA, even under stressed conditions. Overexpression of CLU cDNAs combined with in vitro mutagenesis revealed distinct translational start sites including a so far uncharacterized non-canonical CUG start codon. We show that all exon 2-containing mRNAs encode sCLU and at least three non-glycosylated intracellular isoforms, CLU1449, CLU21449 and CLU34449, which all reside in the cytosol of unstressed and stressed HEK293 cells. The latter is the only form expressed from an alternatively spliced mRNA variant lacking exon 2. Functional analysis revealed that none of these cytosolic CLU forms modulate caspase-mediated intrinsic apoptosis or significantly affects TNF-alpha-induced NF-kappaB-activity. Therefore our data challenge some of the current ideas regarding the physiological functions of CLU isoforms in pathologies.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/3.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.title	Non-secreted clusterin isoforms are translated in rare amounts from distinct human mRNA variants and do not affect bax-mediated apoptosis or the NF-kappaB signaling pathway	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7419	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	PLoS one	de
jgu.journal.volume	8	de
jgu.journal.issue	9	de
jgu.pages.alternative	e75303	de
jgu.publisher.year	2013	-
jgu.publisher.name	PLoS	de
jgu.publisher.place	Lawrence, Kan.	de
jgu.publisher.uri	http://dx.doi.org/10.1371/journal.pone.0075303	de
jgu.publisher.issn	1932-6203	de
jgu.organisation.place	Mainz	-
jgu.identifier.pmid	24073260	-
jgu.subject.ddccode	570	de
opus.date.modified	2018-08-01T10:47:20Z	-
opus.subject.dfgcode	00-000	-
opus.organisation.string	FB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Biochemie	de_DE
opus.identifier.opusid	24283	-
opus.importsource	pubmed	-
opus.institute.number	0907	-
opus.metadataonly	false	-
opus.type.contenttype	Forschungsbericht	de_DE
opus.type.contenttype	Research Report	en_EN
opus.affiliated	Prochnow, Hans	-
opus.affiliated	Rohne, Philipp	-
opus.affiliated	Koch-Brandt, Claudia	-
opus.affiliated	Baiersdörfer, Markus	-
jgu.publisher.doi	10.1371/journal.pone.0075303	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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