Myocardin
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Myocardin is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''MYOCD''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. Myocardin is a
smooth muscle cell Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called becau ...
and
cardiac muscle cell Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the Heart#Wa ...
-specific transcriptional coactivator of
serum response factor Serum response factor, also known as SRF, is a transcription factor protein. Function Serum response factor is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum ...
(SRF). When expressed in smooth muscle precursor cells and abnormally in nonmuscle cells, myocardin can induce smooth muscle
cell differentiation Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...
. Myocardin can also function in the differentiation of myocardial cells.


Structure

Myocardin consists of four distinct regions, one of which is the SAF-A/B, Acinus, and PIAS (SAP) domain. SAP domains are highly conserved motifs containing alpha helices that generally contain hydrophobic, polar, and bulky amino acids. Myocardin also contains a basic region and a glutamine-rich region believed to be involved in binding SRF. Through a series of deletion mutations, researchers have also identified a dimerization motif spanning amino acid residues 513–713, containing an alpha helical leucine zipper analog between residues 513-556.


Function

Myocardin is a transcriptional coactivator, enhancing the activity of specific genes involved in smooth muscle development and function by interacting with transcription factor, SRF. Myocardin can induce smooth muscle
cell differentiation Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...
when it is expressed in appropriate cells. Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in
Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos'' = strange, πους, ''pous'' = foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described with ...
embryos. Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription. Upon its initial discovery, researchers fused myocardin with the well studied GAL 4 transcription factor and examined how the regulation of GAL4-associated genes was affected. Myocardin is believed to activate transcription by binding to CArG box regions of DNA, characterized by the sequence CC(A/T)6GG, of muscle function genes, because mutations to these regions have led to an observed reduction in their sensitivity to myocardin. Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity. Conversely, in smooth muscle cells, myocardin associates with the transcriptional coactivator, p300, stimulting acetylation and consequent expression of smooth muscle cell genes, as well as acetylation of myocardin itself. Class II
HDAC Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important becaus ...
proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin.


Gene

There are four known transcript variants (
isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
) of the MYOCD gene. While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions.
Real-time polymerase chain reaction A real-time polymerase chain reaction (real-time PCR, or qPCR when used quantitatively) is a laboratory technique of molecular biology based on the polymerase chain reaction (PCR). It monitors the amplification of a targeted DNA molecule durin ...
(RT-PCR) have realved two tissue-specific isoforms, myocardin-856, expressed in smooth muscle and found to interact with SRF, and myocardin-935, expressed in cardiac muscle and found to interact with either MEF2 or SRF. Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon. Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found.


References


Further reading

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