SRF

What is SRF Protein?

SRF, or serum response factor, is a nuclear protein part of the big MADS box transcription factor family. It’s key for a bunch of life processes like cell growth, differentiation, cell death, and managing the cell cycle. By latching onto serum response elements (SRE) in gene promoters, SRF helps control the expression of immediate early genes (IEGs) and is crucial in mesoderm development, particularly in growing skeletal muscles. SRF is also tied to many signaling pathways and affects various cell functions. In cardiovascular diseases, SRF plays a big role in controlling genes linked to heart muscle. So, SRF is essential for things like embryonic development, tissue regeneration, muscle growth, and related disease progression.

What is the Function of SRF Protein?

Serum Response Factor (SRF) is a key player in the MADS-box transcription factor family, showing up across various cell types like muscle, endothelial, fibroblast, liver, immune cells, and neurons. It’s crucial for tissue development in the heart, blood vessels, gut, and immune system, and it’s linked to diseases like cardiovascular issues and cancer. SRF docks onto serum response elements (SRE) in gene promoters to control gene transcription that drives important cell functions. It’s involved in helping cells grow, divide, and survive. Plus, it’s essential for developing embryos, muscles, and nervous system tissues, and it interacts with other transcription factors in pathways like Ras-ERK, SP1, ATF6, GATA4, and more, making it central to cell growth, differentiation, and other vital processes.

SRF Related Signaling Pathway

SRF protein is key in pathways involving cell growth, differentiation, stress response, and building the cell’s structure. It teams up with transcription co-factors like TCF, MRTF, and p49/STRAP. For cell growth signals, SRF partners with TCF members, like Elk-1, which get activated by MAPK signals to push cell cycle gene expression. In stress situations, SRF kicks in via p38 MAPK to help transcribe genes like ANF in heart cells. MRTF-SRF interactions are critical for embryo development and cell shape changes, while SRF’s work with p49/STRAP influences mitochondria and cell structure. SRF also links with TEAD and YAP from the Hippo pathway, affecting heart fibrosis and muscle cell changes. Its activation is tweaked by miRNAs and lncRNAs, especially impacting the MRTF-SRF axis for structuring cells and gene control. Hence, SRF pathways are central to managing cell behavior, linking to heart development, disease, and cell-specific actions.

SRF Related Diseases

Serum Response Factor, or SRF, is tightly linked to various diseases, notably heart diseases, cancer, and neurodegenerative conditions. It works by teaming up with various cofactors to regulate genes tied to contractile and actin cytoskeleton structures, crucial for heart and vascular health. Issues with SRF’s transcription activity can lead to congenital heart defects, like Tetralogy of Fallot. In heart diseases, the phosphorylation state of SRF is essential in conditions like pressure-induced hypertrophy and dilated cardiomyopathy. SRF also has a hand in cancer development and spread, though its influence can go both ways, potentially boosting or hindering tumor growth. In neurodegenerative diseases, excessive SRF might be linked to increased contractility in cerebellar arteries, possibly affecting Alzheimer’s. Additionally, SRF plays a role in gut health, and its absence could lead to developmental issues. Thus, SRF is a crucial player in these disorders, offering a significant target for research and treatment.

Bioapplications of SRF

Recombinant SRF protein is a big deal in research, industry, and medicine. In research, it helps us explore crucial biological processes like cell cycles, apoptosis, and embryonic development, as well as regulate the expression of immediate early genes and muscle-specific genes. On the industrial side, cutting-edge biotech methods improve the production efficiency and quality of recombinant proteins, which in turn fuels new treatments and drug development. In medical research, SRF is linked with a variety of diseases, such as cardiovascular issues, cancer, and neurodegenerative disorders. It plays a role in smooth muscle cell phenotype switching and vascular remodeling, and its expression in gastric cancer provides key insights for both disease mechanics research and novel treatment approaches. So overall, recombinant SRF protein is super important for advancing both our scientific understanding and clinical applications in these areas.

Case Study 1: Ni H. et al. Arterioscler Thromb Vasc Biol. 2021

Vascular smooth muscle cell (VSMC) plasticity is key in atherosclerosis, and lncRNAs like CARMN play a role. CARMN, enriched in VSMCs, changes with atherosclerosis progression and is found in both mouse and human plaques. Reducing CARMN in mice led to a 38% decrease in atherosclerotic lesions and a 45% reduction in VSMC proliferation. CARMN influences VSMC behavior independently of miR143/145, interacting with SRF to alter gene expression. Knockdown of SRF eliminates CARMN’s effect on VSMC plasticity, highlighting its significance in this process.

• 
  Fig1. SRF and Histone H3 protein were detected by Western blotting.
• 
  Fig2. Mapping the SRF interaction region of CARMN.

Case Study 2: Li J. et al. Circulation. 2020

Concentric and eccentric cardiac hypertrophy are linked to pressure and volume overload in cardiovascular disease, both raising heart failure risk. These hypertrophy forms show asymmetrical growth in cardiac myocytes, either in width or length. Understanding the mechanisms behind this could uncover new treatments. In studies involving rat myocytes, mice, and human tissue, a pathway was found that controls this uneven growth. It turns out that SRF phosphorylation acts as a switch, balancing myocyte width versus length. RSK3 and PP2A enzymes regulate SRF at signalosomes, influencing growth direction. Blocking these enzymes’ interactions with their scaffold alters cardiac remodeling, potentially guiding new heart failure therapies.

• 
  Fig3. Neonatal myocytes transfected with control or mAKAP siRNA were used for co-immunoprecipitation assay of endogenous SRF-mAKAPβ-PP2A complexes.
• 
  Fig4. Immunoblot signals for phospho-S103 and total SRF antibodies were normalized by total protein content detected by Ponceau S stain.

• 
  Fig1. Model for the role of SRF S103 phosphorylation in the regulation of pathological cardiac hypertrophy. (Jinliang Li, 2020)
• 
  Fig2. TCF21 binding is enriched in SRF targeted loci genome-wide, and binds and inhibits transcription in both the SRF and MYOCD loci. (Manabu Nagao, 2020)

SRF has several biochemical functions, for example, RNA polymerase II core promoter proximal region sequence-specific DNA binding,chromatin DNA binding,histone deacetylase binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SRF itself. We selected most functions SRF had, and list some proteins which have the same functions with SRF. You can find most of the proteins on our site.

Function	Related Protein
contributes_to transcription factor activity, RNA polymerase II core promoter sequence-specific	NKX3-1
transcription factor activity, RNA polymerase II transcription factor binding	SMAD4,ZNF296,ATF2,NACC2,TWIST2,GATA4,GTF2E1,LHX2,HIF1A,MYOCD
transcription factor binding	GNPTAB,TBP,MYC,FIGLA,DIP2B,CCND1,ZEB1,APBB2,SOX8,MECP2
chromatin DNA binding	HIST1H1D,XBP1,EP300,EZH2,HDAC3,INSM1B,FOXC2,NOTCH1,ZIC2,PRDM14
transcription factor activity, sequence-specific DNA binding	ZNF79,HOMEZB,XBP1,HSF2,MXD1,NFE2L1,RORCA,SIX1A,OTX1A,RORB
RNA polymerase II core promoter proximal region sequence-specific DNA binding	NDN,ZNF486,GZF1,BSX,CREB3,TCF3B,RAX,NR3C1,FEZF1,TBX15
histone deacetylase binding	YWHAE,RUNX2,NKX2-5,BRMS1,CBX5,SP2,ANKRA2,HDAC1,PKN1,GMNN
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding	CSRNP1,MYOG,MYOCD,MAF,MAFF,PLAGL1,DMRT1,PKNOX1,GATA4,BARHL1A
protein binding	GABBR2,MED4,PUS7L,CTSK,GCM1,CD80,TBC1D14,LIN37,RHNO1,ZNF649

SRF has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SRF here. Most of them are supplied by our site. Hope this information will be useful for your research of SRF.

MKL2;MKL1;MYOD1;MYOG;MYOCD;ALDH3A1;CIRBP;q8clf6_yerpe