Regulation of the human atrial myosin light chain 1 promoter by Ca<sup>2+</sup>‐calmodulin‐dependent signaling pathways

Woischwill, Christiane; Karczewski, Peter; Bartsch, Holger; Luther, Hans‐Peter; Kott, Monika; Haase, Hannelore; Morano, Ingo

doi:10.1096/fj.04-2201com

Cited by 12 publications

(12 citation statements)

References 33 publications

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“…PP2A levels are increased in differentiated H9C2 cells, and PP2A has been shown to dephosphorylate CaMKIV, inhibiting its activity (37,39). To determine whether HDAC5 nuclear localization in differentiated cells is dependent on PP2A, cells were treated with the PP2A inhibitor okadaic acid for 2 h after the differentiation process.…”

Section: Inhibition Of Camkiv/pkd Results In Change In Yy1 Function Imentioning

confidence: 99%

“…We also showed that PP2A is involved in HDAC5 nuclear localization in differentiated cells. PP2A levels are increased in differentiated cells (11), and PP2A promotes CaMKIV dephosphorylation (36,37). We cannot determine whether HDAC5 nuclear localization in differentiated cells is a direct consequence of PP2A dephosphorylation of HDAC5 or whether it is a consequence of CaMKIV inactivation.…”

Section: Yy1 Functional Domainsmentioning

confidence: 96%

“…H9C2 cells express both CaMKII and CaMKIV (9,37). To test the mechanism of HDAC5 cytoplasmic localization in undifferentiated H9C2 cells, HDAC5-Flag-infected cells were treated for 2 h with 1 M of the general kinase inhibitor K252A (39), 2 M of the CaMKII inhibitor KN-93 (12, 28), 10 M of the PKC inhibitor Bis I, and 10 M of the PKD inhibitor Gö-6976 (34).…”

Section: Hdac5 Cytoplasmic Localization In Undifferentiated Cells Is mentioning

confidence: 99%

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Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Sucharov¹,

Langer²,

Bristow³

et al. 2006

American Journal of Physiology-Cell Physiology

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is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. YY1 is a repressor of transcription in differentiated H9C2 cells and in neonatal cardiac myocytes but an activator of transcription in undifferentiated H9C2 cells. We now present a detailed analysis of the functional domains of YY1 when it is acting as a repressor or an activator and identify the mechanism whereby its function is regulated in the differentiation of H9C2 cells. We show that histone deacetylase 5 (HDAC5) is localized to the cytoplasm in undifferentiated H9C2 cells and that this localization is dependent on Ca 2ϩ /calmodulin-dependent kinase IV (CaMKIV) and/or protein kinase D (PKD). In differentiated cells, HDAC5 is nuclear and interacts with YY1. Finally, we show that HDAC5 localization in differentiated cells is dependent on phosphatase 2A (PP2A). Our results suggest that a signaling mechanism that involves CaMKIV/PKD and PP2A controls YY1 function through regulation of HDAC5 and is important in the maintenance of muscle differentiation. differentiation YY1 IS A UBIQUITOUSLY expressed, highly conserved transcription factor that has been implicated in a variety of cellular processes, including development, where it can function as a polycomb protein (1). Through its interactions with other proteins, YY1 can repress, activate, or initiate transcription from various promoters (for a review, see Ref. 33). Previous work has suggested that YY1 functions primarily as a repressor and that its activator function is dependent on a conformational change that alters its repression domain (4, 13, 14). YY1 has also been shown to displace transcriptional activators from promoters, resulting in transcriptional repression (15,33). Posttranslational modifications of YY1, including acetylation and deacetylation, also play roles in its various functions (38). Acetylation of histones results in derepression of transcription due to an opening of the chromatin structure, whereas deacetylation results in transcription repression. YY1 has been shown to interact with class I histone deacetylases (HDACs) 1, 2, and 3 in HeLa cells (38), and this may be a mechanism of gene regulation shared by YY1 and histones. There are three classes of HDACs (I, II, and III) based on their homology with three structurally and biochemically distinct yeast HDACs (reviewed in Refs. 24 and 25). Muscle cells express all three HDAC classes (40). Localization of class II HDACs is regulated by phosphorylation; they translocate to the cytoplasm when phosphorylated, which results in transcription derepression (22).In muscle cells, YY1 has been shown to repress most muscle-specific genes tested with the exception of the BNP promoter (2, 6, 29). We have recently shown that YY1 represses gene expression and promoter activity of the human and rat ␣-myosin heavy chain (␣-MyHC) gene in cardiac myocytes (21, 32). Interestingly, we showed that repression is dependent on a region of the protein known to interact with...

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Section: Inhibition Of Camkiv/pkd Results In Change In Yy1 Function Imentioning

confidence: 99%

Section: Yy1 Functional Domainsmentioning

confidence: 96%

Section: Hdac5 Cytoplasmic Localization In Undifferentiated Cells Is mentioning

confidence: 99%

See 1 more Smart Citation

Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Sucharov¹,

Langer²,

Bristow³

et al. 2006

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

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“…The dominant role of the Ca 2ϩ -calmodulin-dependent signaling pathway in the regulation of human ELC a expression was shown by Woischwill et al (111). The expression of ELC a in compartments other than the atrium has been associated with a diseased and/or hypertrophied heart (for review see Refs 54 and 65).…”

Section: Atrial Elcmentioning

confidence: 98%

Myosin essential light chain in health and disease

Hernandez¹,

Jones²,

Guzman³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

116

114

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The essential light chain of myosin (ELC) is known to be important for structural stability of the ␣-helical lever arm domain of the myosin head, but its function in striated muscle contraction is poorly understood. Two ELC isoforms are expressed in fast skeletal muscle, a long isoform and its NH 2-terminal ϳ40 amino acid shorter counterpart, whereas only the long ELC is observed in the heart. Biochemical and structural studies revealed that the NH 2-terminus of the long ELC can make direct contacts with actin, but the effects of the ELC on the affinity of myosin for actin, ATPase, force, and the kinetics of force generating myosin cross-bridges are inconclusive. Myosin containing the long ELC has been shown to have slower cross-bridge kinetics than myosin with the short isoform. A difference was also reported among myosins with long isoforms. Increased shortening velocity was observed in atrial compared with ventricular muscle fibers. The common findings suggest that ELC provides the fine tuning of the myosin motor function, which is regulated in an isoform and tissue-dependent manner. The functional importance of the ELC is further implicated by the discovery of ELC mutations associated with Familial Hypertrophic Cardiomyopathy. The pathological phenotypes vary in severity, but more notably, almost all ELC mutations result in sudden cardiac death at a young age. This review summarizes the functional roles of striated muscle ELC in normal healthy muscle and in disease. Transgenic animal models and phenotypic characterization of ELC-mediated remodeling of the heart are also discussed.cross-bridge kinetics; striated muscle contraction; familial hypertrophic cardiomyopathy; sarcomeric mutations; failing heart; sudden cardiac death STRIATED MUSCLE MYOSIN

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“…A proposed mechanism for improved Ca 2+ sensitivity has been that troponins T [22] and I [23] undergo a shift in the isoforms expressed and that atrial myosin light chain 1 increases expression levels [24]. It has also been shown that CaMKII can act to mediate troponin I function [8] and the promoter-region of the atrial myosin light chain-1 gene [25]. It now appears that CaMKII may be able to acutely induce a shift in the myofilament sensitivity to Ca 2+ to a more energetically favorable state after exercise training, although other studies have suggested that PKA mediates Ca 2+ sensitivity [26].…”

Section: Myofilament Ca 2+ Sensitivitymentioning

confidence: 99%

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Kemi

Ellingsen

Ceci

et al. 2007

Journal of Molecular and Cellular Cardiology

113

116

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Cardiac adaptation to aerobic exercise training includes improved cardiomyocyte contractility and calcium handling. Our objective was to determine whether cytosolic calcium/calmodulindependent kinase II and its downstream targets are modulated by exercise training. A six-week aerobic interval training program by treadmill running increased maximal oxygen uptake by 35% in adult mice, whereupon left ventricular cardiomyocyte function was studied and myocardial tissue samples were used for biochemical analysis. Cardiomyocytes from trained mice had enhanced contractility and faster relaxation rates, which coincided with larger amplitude and faster decay of the calcium transient, but not increased peak systolic calcium levels. These changes were associated with reduced phospholamban expression relative to sarcoplasmic reticulum calcium ATPase, and constitutively increased phosphorylation of phospholamban at the threonine 17, but not at the serine 16 site. Calcium-calmodulin-dependent kinase IIδ phosphorylation was increased at Threonine 287, indicating activation. To investigate the physiological role of calcium/ calmodulin-dependent kinase IIδ phosphorylation, this kinase was blocked specifically by autocamtide-2 related inhibitory peptide II. This maneuver completely abolished training-induced improvements of cardiomyocyte contractility and calcium handling, and blunted, but did not completely abolish the training-induced increase in Ca 2+ sensitivity. Also, inhibition of calcium/ calmodulin-dependent kinase II reduced the greater frequency-dependent acceleration of relaxation that was observed after aerobic interval training. These observations indicate that calcium/calmodulin-dependent kinase IIδ contributes significantly to the functional adaptation of the cardiomyocyte to regular exercise training.

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Regulation of the human atrial myosin light chain 1 promoter by Ca²⁺‐calmodulin‐dependent signaling pathways

Cited by 12 publications

References 33 publications

Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Myosin essential light chain in health and disease

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

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Regulation of the human atrial myosin light chain 1 promoter by Ca2+‐calmodulin‐dependent signaling pathways

Cited by 12 publications

References 33 publications

Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A

Myosin essential light chain in health and disease

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

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Regulation of the human atrial myosin light chain 1 promoter by Ca²⁺‐calmodulin‐dependent signaling pathways