Transgelin-2: Biochemical and Clinical Implications in Cancer and Asthma

Actin is a critical component of the cellular cytoskeleton and interacts with a plethora of actin-binding proteins. Transgelin-2 is an important actin-binding protein and misregulation of transgelin-2 may contribute to diseases such as cancer and asthma. Ezrin has emerged as an essential regulator of transgelin-2 in biological functions other than those involving actin. Specific targeting of transgelin-2 may result in a high potential to selectively and effectively regulate various diseases. Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders. Transgelin-2 has been regarded as an actin-binding protein that induces actin gelation and regulates actin cytoskeleton. However, transgelin-2 has recently been shown to relax the myosin cytoskeleton of the airway smooth muscle cells by acting as a receptor for extracellular metallothionein-2. From a clinical perspective, these results support transgelin-2 as a promising therapeutic target for diseases such as cancer and asthma. The inhibition of transgelin-2 prevents actin gelation and thereby cancer cell proliferation, invasion, and metastasis. Conversely, the activation of transgelin-2 with specific agonists relaxes airway smooth muscles and reduces pulmonary resistance in asthma. Here, we review new studies on the biochemical properties of transgelin-2 and discuss their clinical implications for the treatment of immune, oncogenic, and respiratory disorders. proteins bind actin and regulate the functions of actin filaments. actin filaments crosslinked with other proteins to form a gel-like network. the initiation of actin polymerization from free monomers. the rapid conversion of monomeric actin (G-actin or globular-actin) to the polymeric form of actin (F-actin or filamentous-actin). a major structural component of the airway; these play an important role in both normal breathing and pathophysiologic conditions such as asthma. a type of transmembrane protein that mediates in cell–cell adhesion. domain of ezrin that is important for regulating F-actin and intramolecular interaction. member of the mitogen-activated protein kinase family that transmits signals from extracellular agents to regulate extensive cellular processes. a protein that has the ability to interact with both the plasma membrane and actin. domain of ezrin that is required for membrane binding. specific areas that maintain the mature stage of naive lymphocytes and initiate the adaptive immune responses. a heterotrimer consisting of a phosphatase catalytic subunit (PP1Cδ), a myosin phosphatase targeting subunit (MYPT1), and a 20-kDa subunit (M20) that dephosphorylates MLC. the low molecular weight component of myosin; the myosin light chain phosphorylation plays an important role in muscle contraction. the 110-kDa subunit of MLCP that can enhance the catalytic activity and specificity. a family of highly conserved transcription factors that plays a key role in regulating immune response to infection. a striated muscle that is under the voluntary control of the somatic nervous system. an involuntary nonstriated muscle that causes a hollow organ, such as airway smooth muscle, to contract or relax. a multifunctional cytokine that plays a pivotal role in diverse cellular processes.