Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.

Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expressio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sophia Magen, Roberta Magnani, Sitvanit Haziza, Eli Hershkovitz, Robert Houtz, Franca Cambi, Ruti Parvari
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29f6235454214df3a783dfc94003acc2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:29f6235454214df3a783dfc94003acc2
record_format	dspace
spelling	oai:doaj.org-article:29f6235454214df3a783dfc94003acc22021-11-18T08:04:10ZHuman calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.1932-620310.1371/journal.pone.0052425https://doaj.org/article/29f6235454214df3a783dfc94003acc22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23285036/?tool=EBIhttps://doaj.org/toc/1932-6203Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional transcripts in cells of the 2p21 deletion syndrome patients that start from alternative exons positioned outside the deletion region. One of them starts in the 2(nd) known exon, the other in a novel exon. The transcript starting from the novel exon was also identified in a variety of tissues from normal individuals. These new transcripts are not expected to produce proteins. Immunofluorescent localization of tagged CaM KMT in HeLa cells indicates that it is present in both the cytoplasm and nucleus of cells whereas the short isoform is localized to the Golgi apparatus. Using Western blot analysis we show that the CaM KMT protein is broadly expressed in mouse tissues. Finally we demonstrate that the CaM KMT interacts with the middle portion of the Hsp90 molecular chaperon and is probably a client protein since it is degraded upon treatment of cells with the Hsp90 inhibitor geldanamycin. These findings suggest that the CaM KMT is the major, possibly the single, methyltransferase of calmodulin in human cells with a wide tissue distribution and is a novel Hsp90 client protein. Thus our data provides basic information for a gene potentially contributing to the patient phenotype of two contiguous gene deletion syndromes.Sophia MagenRoberta MagnaniSitvanit HazizaEli HershkovitzRobert HoutzFranca CambiRuti ParvariPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52425 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sophia Magen Roberta Magnani Sitvanit Haziza Eli Hershkovitz Robert Houtz Franca Cambi Ruti Parvari Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
description	Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional transcripts in cells of the 2p21 deletion syndrome patients that start from alternative exons positioned outside the deletion region. One of them starts in the 2(nd) known exon, the other in a novel exon. The transcript starting from the novel exon was also identified in a variety of tissues from normal individuals. These new transcripts are not expected to produce proteins. Immunofluorescent localization of tagged CaM KMT in HeLa cells indicates that it is present in both the cytoplasm and nucleus of cells whereas the short isoform is localized to the Golgi apparatus. Using Western blot analysis we show that the CaM KMT protein is broadly expressed in mouse tissues. Finally we demonstrate that the CaM KMT interacts with the middle portion of the Hsp90 molecular chaperon and is probably a client protein since it is degraded upon treatment of cells with the Hsp90 inhibitor geldanamycin. These findings suggest that the CaM KMT is the major, possibly the single, methyltransferase of calmodulin in human cells with a wide tissue distribution and is a novel Hsp90 client protein. Thus our data provides basic information for a gene potentially contributing to the patient phenotype of two contiguous gene deletion syndromes.
format	article
author	Sophia Magen Roberta Magnani Sitvanit Haziza Eli Hershkovitz Robert Houtz Franca Cambi Ruti Parvari
author_facet	Sophia Magen Roberta Magnani Sitvanit Haziza Eli Hershkovitz Robert Houtz Franca Cambi Ruti Parvari
author_sort	Sophia Magen
title	Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
title_short	Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
title_full	Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
title_fullStr	Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
title_full_unstemmed	Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.
title_sort	human calmodulin methyltransferase: expression, activity on calmodulin, and hsp90 dependence.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/29f6235454214df3a783dfc94003acc2
work_keys_str_mv	AT sophiamagen humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT robertamagnani humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT sitvanithaziza humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT elihershkovitz humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT roberthoutz humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT francacambi humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence AT rutiparvari humancalmodulinmethyltransferaseexpressionactivityoncalmodulinandhsp90dependence
_version_	1718422276146200576

Human calmodulin methyltransferase: expression, activity on calmodulin, and Hsp90 dependence.

Ejemplares similares