BIOUNIVERSA s.r.l., R&D Division, Baronissi, SA, 84081, Italy; Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
Semin Cell Dev Biol. 2018 Jun;78:85-92. doi: 10.1016/j.semcdb.2017.08.049. Epub 2017 Aug 31.
BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.
BAG3 是一种多功能蛋白，可通过其 BAG 结构域与热休克蛋白 (Hsp) 70 结合，并通过其 WW 结构域、富含脯氨酸 (PXXP) 重复序列和 IPV (Ile-Pro-Val) 基序与其他伙伴结合。其细胞内表达可被应激刺激诱导，而在骨骼肌、心肌细胞和几种肿瘤类型中则为组成型表达。BAG3 可调节其伙伴蛋白的水平、定位或活性，从而调节主要的细胞途径和功能，包括细胞凋亡、自噬、机械转导、细胞骨架组织、运动。在对胰腺导管腺癌 (PDAC) 的研究中，已经鉴定出 BAG3 的一种分泌形式。分泌型 BAG3 可以与巨噬细胞上表达的特定受体 IFITM2 结合，并诱导释放维持肿瘤生长和转移过程的因子。因此，BAG3 中和似乎构成了 PDAC 及其他肿瘤治疗的一种新的潜在策略。
