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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The predominant response of the heart to sustained increased work load is development of ventricular hypertrophy, principally as a result of hypertrophy of cardiomyocytes. The molecular mechanisms and factors involved in cardiomyocyte hypertrophy are poorly understood. Myotrophin is a novel 12-kilodalton protein recently implicated as a factor associated with and able to induce cardiac hypertrophy. Cloning of rat myotrophin revealed that this protein is identical to the functionally undefined rat, murine and chicken V-1 proteins. Although human myotrophin has been purified to homogeneity, its gene has not been characterized. In this report we describe the cloning, expression, purification and characterization of the human homolog of myotrophin/V-1 protein. Sequence analysis indicators high homology (>90%) between all species at both the nucleotide and amino acid levels, and Southern blot analysis of genomic DNA from diverse species verifies that myotrophin/V-1 is a highly conserved gene. Northern analysis indicates wide-spread expression of a single human transcript, and examination of mRNA distribution in 50 human tissues by dot blot analysis indicates ubiquitous expression with relatively high expressioon in adult and fetal heart. We verify that recombinant human myotrophin produces cardiomyocyte hypertrophy, and we demonstrate for the first time that elevated levels of myotrophin/V-1 protein mRNA are expressed in human dilated cardiomyopathic hearts. We report the novel findings that myotrophin expression is elevated in ischemic hearts, and that myotrophin expression correlates positively with ventricular mass in a hypoxic rat model of induced right ventricular hypertrophy.
J Mol Cell Cardiol 1999 Apr
PMID:cDNA sequence and characterization of the gene that encodes human myotrophin/V-1 protein, a mediator of cardiac hypertrophy. 1032 99

Proteins containing stretches of repeating amino acid sequences are prevalent throughout nature, yet little is known about the general folding and assembly mechanisms of these systems. Here we propose myotrophin as a model system to study the folding of ankyrin repeat proteins. Myotrophin is folded over a large pH range and is soluble at high concentrations. Thermal and urea denaturation studies show that the protein displays cooperative two-state folding properties despite its modular nature. Taken together with previous studies on other ankyrin repeat proteins, our data suggest that the two-state folding pathway may be characteristic of ankyrin repeat proteins and other integrated alpha-helical repeat proteins in general.
J Mol Biol 2002 Jul 05
PMID:Equilibrium folding and stability of myotrophin: a model ankyrin repeat protein. 1207 76

Hemodynamic load is a major determinant of cardiac mass and its phenotype, but very little is known about how mechanical load is converted into intracellular signals of gene expression and regulation. We have shown earlier that factors other than blood pressure control play a role in the mechanism involved in the development or regression of myocardial hypertrophy. We have identified a soluble factor, myotrophin, from the hearts of spontaneously hypertensive rats and dilated cardiomyopathic humans, which stimulates protein synthesis both in neonatal and adult rat cardiac myocytes. Myotrophin gene has been mapped and shown to be a novel gene localized in human chromosome 7q-33. The present study was conducted to evaluate the mechanism by which myotrophin is released and in turn initiates myocardial hypertrophy. We used an in vitro model, where neonatal cardiac myocytes were grown on stretchable plates and examined the effect of stretch on myotrophin gene expression (to mimic pressure overload), an in vivo model using beating non-working hearts exposed to high pressure and three different models of hypertensive rats. Our data showed that both cyclic stretch and exposure to high pressure caused significant increase in the transcript levels of myotrophin followed by expression of beta-myosin heavy chain and atrial natriuretic factor associated with an increase in myocardial protein synthesis. All three models of hypertensive rats also showed a significant increase in myotrophin transcripts. Altogether, our data strongly suggest that stretching of the cells by pressure or volume turns on the myotrophin, which in turn is responsible for the initiation process of myocardial hypertrophy in response to pressure or volume overload.
Mol Cell Biochem 2004 Jul
PMID:Regulation of myotrophin gene by pressure overload and stretch. 1553 12

The 118 residue protein myotrophin is composed of four ankyrin repeats that stack linearly to form an elongated, predominantly alpha-helical structure. The protein folds via a two-state mechanism at equilibrium. The free energy change of unfolding in water (DeltaG(U-N)(H(2)O)) is 5.8 kcal.mol(-1). The chevron plot reveals that the folding reaction has a broad energy barrier and that it conforms to a two-state mechanism. The rate of folding in water (k(f)(H(2)O)) of 95 s(-1) is several orders of magnitude slower than the value predicted by topological calculations. Proline mutants were used to show that the minor kinetic phases observed for myotrophin arise from heterogeneity of the ground states due to cis-trans isomerisation of prolyl as well as non-prolyl peptide bonds. Myotrophin is the first example of a naturally occurring ankyrin repeat protein that conforms to an apparent two-state mechanism at equilibrium and under kinetic conditions, making it highly suitable for high resolution protein folding studies.
J Mol Biol 2007 Jan 26
PMID:Biophysical characterisation of the small ankyrin repeat protein myotrophin. 1711 3

The ankyrin repeat is a protein module with high affinity for other ankyrin repeats based on strong Van der Waals forces. The resulting dimerization is unusually resistant to both mechanical forces and alkanization, making this module exceedingly useful for meeting the extraordinary demands of muscle physiology. Many aspects of muscle function are controlled by the superfamily ankyrin repeat domain containing proteins, including structural fixation of the contractile apparatus to the muscle membrane by ankyrins, the archetypical member of the family. Additionally, other ankyrin repeat domain containing proteins critically control the various differentiation steps during muscle development, with Notch and developmental stage-specific expression of the members of the Ankyrin repeat and SOCS box (ASB) containing family of proteins controlling compartment size and guiding the various steps of muscle specification. Also, adaptive responses in fully formed muscle require ankyrin repeat containing proteins, with Myotrophin/V-1 ankyrin repeat containing proteins controlling the induction of hypertrophic responses following excessive mechanical load, and muscle ankyrin repeat proteins (MARPs) acting as protective mechanisms of last resort following extreme demands on muscle tissue. Knowledge on mechanisms governing the ordered expression of the various members of superfamily of ankyrin repeat domain containing proteins may prove exceedingly useful for developing novel rational therapy for cardiac disease and muscle dystrophies.
Crit Rev Biochem Mol Biol 2010 Aug
PMID:Anchoring skeletal muscle development and disease: the role of ankyrin repeat domain containing proteins in muscle physiology. 2051 17

Myotrophin (MTPN) is an effective growth factor in promoting skeletal muscle growth in vitro and vivo and has been purified from porcine skeletal muscle. However, in pigs, the information on MTPN gene is very limited. In this study, we cloned cDNA sequences and analyzed the genomic structure of porcine MTPN gene. The deduced amino acid sequence of porcine MTPN contains two the ankyrin repeat domains. RT-PCR analysis revealed that porcine MTPN gene was widely expressed in many tissues, a high expression level was observed in the spleen, liver and uterus, and transient transfection indicated that porcine MTPN proteins was located in cytoplasms within Pig Kidney Epithelial cells (PK15). Quantitative real-time PCR (qRT-PCR) analyses showed that MTPN expression peaked at embryonic 65 day post conception (dpc). During postnatal muscle development, MTPN expression was down-regulated from the 3 day to the 180 day in Yorkshire pigs. This result suggests that the MTPN gene may be important gene for skeletal muscle growth and provides useful information for further studies on its roles in porcine skeletal muscle.
Mol Biol Rep 2012 Mar
PMID:Molecular characterization, expression patterns and subcellular localization of Myotrophin (MTPN) gene in porcine skeletal muscle. 2166 49