Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2 and CALMS

Toutenhoofd, Sonja L.; Foletti, Davide; Wicki, Roland; Rhyner, Johannes A.; García, Fernando; Tolón, Rosa M.; Strehler, Emanuel E.

doi:10.1016/s0143-4160(98)90028-8

Cited by 63 publications

(38 citation statements)

References 48 publications

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“…The apoCI is a component of very low-density lipoprotein (VLDL) and high density lipoprotein (HDL) that is predominantly expressed in the liver, although it has been shown to be expressed in the testis (28). Calmodulin is a ubiquitously expressed and abundant Ca 2ϩ -binding protein that functions in many cellular processes, including transcriptional regulation through CaM kinase and the transcription factor CREB (29).…”

Section: Resultsmentioning

confidence: 99%

Project normal: Defining normal variance in mouse gene expression

Pritchard

Hsu

Delrow

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

230

164

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The mouse has become an indispensable and versatile model organism for the study of development, genetics, behavior, and disease. The application of comprehensive gene expression profiling technologies to compare normal and diseased tissues or to assess molecular alterations resulting from various experimental interventions has the potential to provide highly detailed qualitative and quantitative descriptions of these processes. Ideally, to interpret experimental data, the magnitude and diversity of gene expression for the system under study should be well characterized, yet little is known about the normal variation of mouse gene expression in vivo. To assess natural differences in murine gene expression, we used a 5406-clone spotted cDNA microarray to quantitate transcript levels in the kidney, liver, and testis from each of 6 normal male C57BL6 mice. We used ANOVA to compare the variance across the six mice to the variance among four replicate experiments performed for each mouse tissue. For the 6 kidney samples, 102 of 3,088 genes (3.3%) exhibited a statistically significant mouse variance at a level of 0.05. In the testis, 62 of 3,252 genes (1.9%) showed statistically significant variance, and in the liver, there were 21 of 2,514 (0.8%) genes with significantly variable expression. Immune-modulated, stress-induced, and hormonally regulated genes were highly represented among the transcripts that were most variable. The expression levels of several genes varied significantly in more than one tissue. These studies help to define the baseline level of variability in mouse gene expression and emphasize the importance of replicate microarray experiments.DNA microarray ͉ variation ͉ transcript ͉ ANOVA T he use of DNA microarrays to obtain qualitative and quantitative profiles of gene expression has increased dramatically over the past several years. Microarrays can provide rapid and accurate measurements of thousands of distinct transcripts simultaneously. Most of the microarray expression studies performed to date have used relatively controlled systems that are manipulable in vitro, such as single-cell organisms (e.g., yeast) and clonal cell lines (1-3). The technology has also been applied to more complex in vivo systems involving mammalian tissues and organs. Many of these studies have been performed by using the mouse as a model organism, in part because of the relative ease of genetic manipulation coupled with the extensive genomic, anatomical, and physiological synteny with humans.

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Section: Resultsmentioning

confidence: 99%

Project normal: Defining normal variance in mouse gene expression

Pritchard

Hsu

Delrow

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

230

164

View full text Add to dashboard Cite

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“…To the best of our knowledge, the involvement of the CALM1P2 gene in the pathogenesis of ADC has not been previously described; however, genetic mutations of CALM genes are observed in other types of cancer (28,29). Toutenhoofd et al (28) concluded that the CALM gene family is differentially active at the transcriptional level in teratoma cells and that the 5' untranslated regions are required to recover full promoter activation. Furthermore, Stanislaus et al (29) suggested that the CALM1 and PLCG2 signaling pathways are the two potential targets for gene knockdown in doxorubicin-and paclitaxel-based chemotherapy of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Characterization of amplification patterns and target genes on the short arm of chromosome 7 in early-stage lung adenocarcinoma

Kang

2013

Molecular Medicine Reports

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Abstract. Chromosomal alterations are a predominant genomic force contributing to the development of lung adenocarcinoma (ADC). High density genomic arrays were conducted to identify critical genetic landmarks that may be important mediators in the formation or progression of early-stage ADC. In this study, the most noteworthy and consistent observation was a copy number gain on the short arm of chromosome 7, which was detected in 85.7% (12/14) of cases. Notably, three distinct regions of amplification were identified between the 7p22.3 and q11.2 regions in 28.6% (4/14) of cases; at a size of 4.1 Mbp (7p22.3-p21.1), 2.6 Mbp (7p15.2-p14.1) and 1.5 Mbp (7p12.3-p11.2). Variations of the 7p11.2 locus that encodes EGFR are known to be oncogenic. Furthermore, potential target genes were identified that were previously not assumed to be involved in the pathogenesis of ADC, including CALM1P2 (7p11.2), HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 (7p15.2) and LOC442586, LOC442589, LOC442282, FAM20C and LOC442651 (7p22.3). The present study determined critical regions on the 7p arm of chromosome 7, which were implicated in ADC. The pattern of rearrangements on the 7p arm may be a consequence of the high density of potential targets and the identified genes at the 7p regions may aid in the development of therapeutic targets for ADC.

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“…This finding has introduced the unusual concept of multiple genes -one protein, and has raised interesting questions concerning the evolution and functional significance of the CALM gene family. In subsequent work, the Strehler group has characterized all three human CALM genes [24,25] (before the advent of the human genome sequence), and in the process, has discovered multiple CALM pseudogenes [26] , as well as an intriguing intronless calmodulin-like gene [27] (see below). Dr. Strehler's group also has provided the first analysis of all three CALM gene promoters and a direct comparison of their relative transcriptional strengths [25] .…”

Section: Alternative Splicing Controls the Membrane Targeting Of Pmcamentioning

confidence: 99%

“…In subsequent work, the Strehler group has characterized all three human CALM genes [24,25] (before the advent of the human genome sequence), and in the process, has discovered multiple CALM pseudogenes [26] , as well as an intriguing intronless calmodulin-like gene [27] (see below). Dr. Strehler's group also has provided the first analysis of all three CALM gene promoters and a direct comparison of their relative transcriptional strengths [25] . This work is significant in that it has opened the way for future studies on the differential regulation of the human CALM gene family in normal and pathological situations.…”

Section: Alternative Splicing Controls the Membrane Targeting Of Pmcamentioning

confidence: 99%

Emanuel Strehler’s work on calcium pumps and calcium signaling

Strehler¹

2011

WJBC

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Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer's disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research area revolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.

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Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2 and CALMS

Cited by 63 publications

References 48 publications

Project normal: Defining normal variance in mouse gene expression

Project normal: Defining normal variance in mouse gene expression

Characterization of amplification patterns and target genes on the short arm of chromosome 7 in early-stage lung adenocarcinoma

Emanuel Strehler’s work on calcium pumps and calcium signaling

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