Kim Hye-Ran, Park Jeong-Su, Karabulut Hatice, Yasmin Fatima, Jun Chang-Duk
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
Immune Synapse and Cell Therapy Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
Front Cell Dev Biol. 2021 Apr 8;9:606149. doi: 10.3389/fcell.2021.606149. eCollection 2021.
Transgelin-2, a small actin-binding protein, is the only transgelin family member expressed in immune cells. In T and B lymphocytes, transgelin-2 is constitutively expressed, but in antigen-presenting cells, it is significantly upregulated upon lipopolysaccharide stimulation. Transgelin-2 acts as a molecular staple to stabilize the actin cytoskeleton, and it competes with cofilin to bind filamentous (F)-actin. This action may enable immune synapse stabilization during T-cell interaction with cognate antigen-presenting cells. Furthermore, transgelin-2 blocks Arp2/3 complex-nucleated actin branching, which is presumably related to small filopodia formation, enhanced phagocytic function, and antigen presentation. Overall, transgelin-2 is an essential part of the molecular armament required for host defense against neoplasms and infectious diseases. However, transgelin-2 acts as a double-edged sword, as its expression is also essential for a wide range of tumor development, including drug resistance and metastasis. Thus, targeting transgelin-2 can also have a therapeutic advantage for cancer treatment; selectively suppressing transgelin-2 expression may prevent multidrug resistance in cancer chemotherapy. Here, we review newly discovered molecular characteristics of transgelin-2 and discuss clinical applications for cancer and immunotherapy.
凝溶胶蛋白-2是一种小的肌动蛋白结合蛋白，是在免疫细胞中表达的唯一凝溶胶蛋白家族成员。在T淋巴细胞和B淋巴细胞中，凝溶胶蛋白-2组成性表达，但在抗原呈递细胞中，脂多糖刺激后其表达显著上调。凝溶胶蛋白-2作为一种分子钉来稳定肌动蛋白细胞骨架，它与丝切蛋白竞争结合丝状（F）-肌动蛋白。这一作用可能在T细胞与同源抗原呈递细胞相互作用期间使免疫突触稳定。此外，凝溶胶蛋白-2阻断Arp2/3复合物介导的肌动蛋白分支，这可能与小丝状伪足形成、增强的吞噬功能和抗原呈递有关。总体而言，凝溶胶蛋白-2是宿主抵御肿瘤和传染病所需分子武器的重要组成部分。然而，凝溶胶蛋白-2是一把双刃剑，因为其表达对包括耐药性和转移在内的多种肿瘤发展也至关重要。因此，靶向凝溶胶蛋白-2在癌症治疗中也可能具有治疗优势；选择性抑制凝溶胶蛋白-2表达可能预防癌症化疗中的多药耐药性。在此，我们综述凝溶胶蛋白-2新发现的分子特征，并讨论其在癌症和免疫治疗中的临床应用。
