Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets.
Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets.
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DOI：
10.3390/ijms19020368
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发表时间：
2018-01-26
影响因子：
5.6
通讯作者：
Quick QA
中科院分区：
文献类型：
--
作者：
Quick QA
斑蛋白是七种细胞骨架交联蛋白（微管-肌动蛋白交联因子1（MACF）、大疱性类天疱疮抗原（BPAG 1）桥粒斑蛋白、包斑蛋白、周斑蛋白、网蛋白、epiplakin）的家族，其将构成细胞骨架的三种主要细丝网络化。已发现Plakins参与归因于这些大分子的自身免疫应答和遗传改变的皮肤、心脏、神经系统和癌症的病症和疾病。尽管它们在多种疾病中的作用和参与，但目前还没有专门针对该蛋白质家族成员的药物或药理学试剂。相反，微管传统上被用于治疗疾病如癌症的微管抑制剂靶向，尽管其具有与其临床用途相关的有害毒性。结构生物信息学研究合作实验室（RCSB）用于鉴定靶向斑蛋白的治疗药物，特别是含有微管结合结构域的斑蛋白MACF 1和BPAG 1。RCSB分析显示，斑蛋白有329种配体，其中超过50%是MACF 1和BPAG 1配体，10种在临床或实验上被证明具有抗癌、抗炎和抗生素等多种治疗应用。
Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted by microtubule inhibiting agents, used for the treatment of diseases such as cancer, in spite of the deleterious toxicities associated with their clinical utility. The Research Collaboratory for Structural Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329 ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were documented, clinically or experimentally, to have several therapeutic applications as anticancer, anti-inflammatory, and antibiotic agents.
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影响因子：
6.4
作者：
Arai, Eri;Sakamoto, Hiromi;Ichikawa, Hitoshi;Totsuka, Hirohiko;Chiku, Suenori;Gotoh, Masahiro;Mori, Taisuke;Nakatani, Tamao;Ohnami, Sumiko;Nakagawa, Tohru;Fujimoto, Hiroyuki;Wang, Linghua;Aburatani, Hiroyuki;Yoshida, Teruhiko;Kanai, Yae
通讯作者：
Kanai, Yae
影响因子：
10.5
作者：
Andra, K;Lassmann, H;Wiche, G
通讯作者：
Wiche, G
影响因子：
3.3
作者：
Bulgaru, Anca M;Mani, Sridhar;Perez-Soler, Roman
通讯作者：
Perez-Soler, Roman
影响因子：
5.6
作者：
Al-Jassar, Caezar;Knowles, Timothy;Chidgey, Maytyn
通讯作者：
Chidgey, Maytyn
影响因子：
20.1
作者：
Angst, BD;Khan, LUR;Gourdie, RG
通讯作者：
Gourdie, RG