CTF1

What is CTF1 protein?

CTF1 (cardiotrophin 1) gene is a protein coding gene which situated on the short arm of chromosome 16 at locus 16p11. The CCAAT-box binding protein 1 (CTF1, also called NF-I or NF-1) is a proline-rich transcription activator. It selectively activates transcription of genes that contain GCCAAT consensus sequence in promoter region, including human Ha-Ras, alpha-globin, hsp70 and many other cellular and viral genes (1, 3-5). Cloning and functional characterization of the protein revealed that CTF1 contains an N-terminal DNA binding domain and a C-terminal proline-rich activation domain. The CTF1 protein is consisted of 201 amino acids and its molecular mass is approximately 21.2 kDa.

What is the function of CTF1 protein?

CTF1 protein is expressed in the heart, it can promote the survival of cardiomyocytes, reduce ischemia/reperfusion injury, and has a protective effect on cardiomyocytes. CTF1 is involved in the regulation of cardiac remodeling, including adaptive changes in cardiac structure and function. CTF1 protein is also involved in the formation of new blood vessels and the regulation of inflammation.

CTF1 Related Signaling Pathway

JAK/STAT signaling pathway: CTF1 binds to GP130 and LEPR to activate the associated JAK kinase, which leads to the phosphorylation and activation of STAT protein.

MAPK/ERK signaling pathway: In addition to activating JAK/STAT, CTF1 activates the MAPK/ERK (mitogen-activated protein kinase/Extracellular signal-regulated kinase) signaling pathway through GP130 and other related proteins.

PI3K/AKT signaling pathway: CTF1 can also affect AKT (protein kinase B) activity by activating PI3K (phosphatidylinositol 3-kinase).

Fig1. Proposed signaling cascade mediating CT-1-induced cell migration. (Darren H Freed, 2011)

CTF1 Related Diseases

CTF1 is mainly expressed in cardiomyocytes and plays a role in the physiological and pathological processes of the heart. It belongs to the IL-6/CNTF (Interleukin-6 / ciliary neurotrophic factor) family and has multiple biological functions, including promoting the survival, proliferation, and differentiation of cardiomyocytes, and the ability to regulate the heart's response to stress. Due to these functions, CTF1 protein is associated with a variety of heart diseases, mainly including: heart failure, coronary artery disease, myocarditis and so on.

Bioapplications of CTF1

Because CTF1 has a protective effect on the heart muscle, CTF1 protein or its mimics are being investigated as potential therapeutic agents for the treatment of cardiovascular diseases, such as myocardial infarction and heart failure. The pro-proliferative and anti-apoptotic properties of CTF1 make it a candidate molecule for cardiac tissue engineering and regenerative medicine that may promote myocardial repair and regeneration.

Case Study 1: Mohammad Abdul-Ghani, 2017

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. The researchers identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

Fig1. Primary neonatal cardiomyocytes were stimulated for 24 h with hCT1 (0.5 nM), PE (100 μM), hCT1 and PE, or control serum-free medium (Ctrl, SF) followed by morphometric analysis.

Fig2. Significant differences were observed between the PAH-induced SUHx rat groups (hCT1 or PBS) and the control rat group.

Case Study 2: Darren H Freed, 2011

Chemotactic movement of myofibroblasts is recognized as a common means for their sequestration to the site of tissue injury. Following myocardial infarction (MI), recruitment of cardiac myofibroblasts to the infarct scar is a critical step in wound healing. Contractile myofibroblasts express embryonic smooth muscle myosin, α-smooth muscle actin, as well as collagens I and III. The researchers examined the effects of cardiotrophin-1 (CT-1) in the induction of primary rat ventricular myofibroblast motility. Changes in membrane potential (E(m)) and Ca(2+) entry were studied to reveal the mechanisms for induction of myofibroblast migration. CT-1-induced cardiac myofibroblast cell migration, which was attenuated through the inhibition of JAK2 (25 μM AG490), and myosin light chain kinase (20 μM ML-7). Inhibition of K(+) channels (1 mM tetraethylammonium or 100 μM 4-aminopyridine) and nonselective cation channels by 10 μM gadolinium (Gd(3+)) significantly reduced migration in the presence of CT-1. CT-1 treatment caused a significant increase in myosin light chain phosphorylation, which could be inhibited by incubation in Ca(2+)-free conditions or by application of AG490, ML-7, and W7 (100 μM; calmodulin inhibitor).

Fig3. CT-1 induces phosphorylation of MLC. Cardiac ventricular myofibroblasts were stimulated with CT-1 (10 ng/ml = 0.37 nM).

Fig4. Effect of CT-1 on membrane potential.

CTF1 has several biochemical functions, for example, cytokine activity,leukemia inhibitory factor receptor binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CTF1 itself. We selected most functions CTF1 had, and list some proteins which have the same functions with CTF1. You can find most of the proteins on our site.

CTF1 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 CTF1 here. Most of them are supplied by our site. Hope this information will be useful for your research of CTF1.

MAGEA6