Control of SERCA2a Ca2+ pump mRNA stability by nuclear proteins: role of domains in the 3′-untranslated region

Misquitta, Christine; Ghosh, Paromita; Mwanjewe, James; Grover, Ashok K.

doi:10.1016/j.ceca.2004.06.003

Cited by 7 publications

(1 citation statement)

References 31 publications

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“…Although the identity of the factors implied in the splicing mechanisms of SERCA2 are not known, it is reasonable to think that protein factors that bind to sequences rich in pyrimidines may be candidates to bind the ISS sequences present in the 3'-flanking region of intron 21 of the SERCA2 gene. Thus, it is possible that splicing factors have a role as part of a constituent mechanism of exon selection; the splicing factors that participate in alternative splicing of SERCA2 pre-mRNA in the cardiac myocyte have to be experimentally identified (Misquitta et al 2005). The 3'-untranslated region of the SERCA2a mRNA contains 5 adenylate-uridylate (AU)-rich regions.…”

Section: Structure Of the Serca Gene And Alternative Splicingmentioning

confidence: 99%

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Zarain‐Herzberg

2006

Can. J. Physiol. Pharmacol.

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The sarcoplasmic reticulum (SR) plays a central role in the contraction and relaxation coupling in the myocardium. The SR Ca(2+)-ATPase (SERCA2) transports Ca(2+) inside the SR lumen during relaxation of the cardiac myocyte. It is well known that diminished contractility of the hypertrophic cardiac myocyte is the main factor of ventricular dysfunction in the failing heart. A key feature of the failing heart is a decreased content and activity of SERCA2, which is the cause of some of the physiological defects observed in the hypertrophic cardiomyocyte performance that are important during transition of compensated hypertrophy to heart failure. In this review different possible mechanisms responsible for decreased transcriptional regulation of the SERCA2 gene are examined, which appear to be the primary cause for decreased SERCA2 expression in heart failure. The experimental evidence suggests that several signalling pathways are involved in the downregulation of SERCA2 expression in the hypertrophic and failing cardiomyocyte. Therapeutic upregulation of SERCA2 expression using replication deficient adenoviral expression vectors, pharmacological interventions using thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel metabolically active compounds are currently under investigation for the treatment of uncompensated cardiac hypertrophy and heart failure.

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Section: Structure Of the Serca Gene And Alternative Splicingmentioning

confidence: 99%

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Zarain‐Herzberg

2006

Can. J. Physiol. Pharmacol.

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Factors controlling the activity of the SERCA2a pump in the normal and failing heart

et al. 2009

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Heart failure is the leading cause of death in western countries and is often associated with impaired Ca(2+) handling in the cardiomyocyte. In fact, cardiomyocyte relaxation and contraction are tightly controlled by the activity of the cardiac sarco(endo)plasmic reticulum (ER/SR) Ca(2+) pump SERCA2a, pumping Ca(2+) from the cytosol into the lumen of the ER/SR. This review addresses three important facets that control the SERCA2 activity in the heart. First, we focus on the alternative splicing of the SERCA2 messenger, which is strictly regulated in the developing heart. This splicing controls the formation of three SERCA2 splice variants with different enzymatic properties. Second, we will discuss the role and regulation of SERCA2a activity in the normal and failing heart. The two well-studied Ca(2+) affinity modulators phospholamban and sarcolipin control the activity of SERCA2a within a narrow window. An aberrantly high or low Ca(2+) affinity is often observed in and may even trigger cardiac failure. Correcting SERCA2a activity might therefore constitute a therapeutic approach to improve the contractility of the failing heart. Finally, we address the controversies and unanswered questions of other putative regulators of the cardiac Ca(2+) pump, such as sarcalumenin, HRC, S100A1, Bcl-2, HAX-1, calreticulin, calnexin, ERp57, IRS-1, and -2.

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Control of protein expression through mRNA stability in calcium signalling

2006

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Control of SERCA2a Ca2+ pump mRNA stability by nuclear proteins: role of domains in the 3′-untranslated region

Cited by 7 publications

References 31 publications

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Factors controlling the activity of the SERCA2a pump in the normal and failing heart

Control of protein expression through mRNA stability in calcium signalling

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Control of SERCA2a Ca2+ pump mRNA stability by nuclear proteins: role of domains in the 3′-untranslated region

Cited by 7 publications

References 31 publications

Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Factors controlling the activity of the SERCA2a pump in the normal and failing heart

Control of protein expression through mRNA stability in calcium signalling

Contact Info

Product

Resources

About

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.

Regulation of the sarcoplasmic reticulum Ca²⁺-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.