TWEAK/TNFSF12 蛋白, Human (CHO)

TWEAK Protein refers to the cytokine tumor necrosis factor-like weak inducer of apoptosis, belongs to tumor necrosis factor (TNF) superfamily. TWEAK protein binds to FN14 and TNRFSF12/APO3, is a weak inducer of apoptosis^[1]. TWEAK does have pro-apoptotic activity for tumor cell, mediates NF-kappa-B activation, promotes angiogenesis and the proliferation of endothelial cells (ECs)^[2]. TWEAK also increases IL-6 and IL-8 secretion, and could potentiate the pro-inflammatory activities of TNF and IL-1^[3]. Human TWEAK protein is a type II transmembrane protein (M1-H249) with a transmembrane domain (22-42 a.a.). TWEAK/TNFSF12 Protein, Human (CHO) is the extracellular part (R99-H249) of TWEAK protein, produced by CHO cells with tag free.

TWEAK蛋白是指细胞因子肿瘤坏死因子样细胞凋亡弱诱导剂。它是属于肿瘤坏死因子（TNF）超家族的多功能细胞因子，通过结合TweakR/Fn14受体发挥作用。TWEAK 是一种细胞表面相关的 II 型跨膜蛋白，具有 2 种类型的蛋白链：膜形式和分泌或可溶形式。可溶形式通过蛋白水解加工从膜形式衍生而来。人和小鼠的蛋白质序列差异很大，相似度为 24.79%^[1]。
TWEAK 与 FN14 结合，也可能与 TNRFSF12/APO3 结合，是某些细胞凋亡的弱诱导剂。细胞类型。TWEAK 介导 NF-kappa-B 激活，促进血管生成和内皮细胞增殖^[2]。
TWEAK 具有多种生物活性，其中许多与免疫系统发育和功能相关< super>[1]。
TWEAK 对一组选定的人类肿瘤细胞系和单核细胞具有促凋亡活性，同时促进人类血管 EC 和 SMC 中的细胞增殖。此外，FGF-2 共同治疗可以增强 TWEAK 刺激的 HUVEC 增殖，这种作用可能是由于 FGF-2 上调 TweakR/Fn14 基因表达的能力所致。同时，TWEAK-TweakR/Fn14 自分泌信号传导促进人微血管肾内皮细胞 (HMREC) 迁移^[1]。
TWEAK 在炎症反应中也发挥着关键作用。TWEAK 可刺激人类肿瘤细胞系、WI-38 成纤维细胞和星形胶质细胞中白细胞介素 (IL)-8 的分泌。TWEAK 还可以增加星形胶质细胞中 IL-6 的分泌和 ICAM-1 的表达。此外，TWEAK 共孵育可增强 TNF 和 IL-1 的促炎活性，推测 TWEAK 可能参与慢性炎症性疾病的发病机制^[3]。
总之，TWEAK 涉及刺激细胞生长和血管生成、诱导炎症细胞因子，并在某些实验条件下刺激细胞凋亡^[1]。

TWEAK (human; 100 ng/mL; changed media 3 times per week for 4 weeks) induces matrix metalloprotease (MMP) production in human chondrocytes^[4].
TWEAK (human; 500 ng/mL; 24 h) and Fn14 interaction induces upregulation of ICAM-1 and E-selectin on HUVEC, also induces chemokine secretion by HUVEC^[5].
TWEAK (human; 10-1000 ng/mL; 24-72 h) induces MCP-1 production in HMC in a dose- and time-dependent manner^[6].

Fc-TWEAK (human; 200 μg/mouse; i.p.; twice weekly, dose at 0, 4, and 7 days) induces inflammatory gene expression and kidney cell proliferation in vivo in C57Bl/6 mice^[6].

1.The ED₅₀ is <1 ng/mL as measured in a cell cytotoxicity assay using HTB-38 (HT-29) cells.
2.Measured in a cell proliferation assay using HUVEC human umbilical vein endothelial cells. The ED₅₀ for this effect is 2.53 ng/mL.

• 
  Measured in a cell proliferation assay using HUVEC human umbilical vein endothelial cells. The ED₅₀ for this effect is 2.53 ng/mL, corresponding to a specific activity is 3.953×10⁵ U/mg.

Human

CHO

Tag Free

O43508-1/Q4ACW9 (R99-H249)

8742  [NCBI]

RKTRARRAIAAHYEVHPRPGQDGAQAGVDGTVSGWEEARINSSSPLRYNRQIGEFIVTRAGLYYLYCQVHFDEGKAVYLKLDLLVDGVLALRCLEEFSATAASSLGPQLRLCQVSGLLALRPGSSLRIRTLPWAHLKAAPFLTYFGLFQVH

Approximately 20-22 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.

<0.2 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Wiley SR, et al. TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor. Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):241-9.  [Content Brief]

  [2]. Maecker H, et al. TWEAK attenuates the transition from innate to adaptive immunity. Cell. 2005 Dec 2;123(5):931-44.  [Content Brief]

  [3]. Lammens A, et al. Crystal structure of human TWEAK in complex with the Fab fragment of a neutralizing antibody reveals insights into receptor binding. PLoS One. 2013 May 8;8(5):e62697.  [Content Brief]

  [4]. TNFSF12 TNF superfamily member 12 [Homo sapiens (human)]

  [5]. Lynch CN, et al. TWEAK induces angiogenesis and proliferation of endothelial cells. J Biol Chem. 1999 Mar 26;274(13):8455-9.  [Content Brief]

  [6]. Lynch CN, et al. TWEAK induces angiogenesis and proliferation of endothelial cells. J Biol Chem. 1999 Mar 26;274(13):8455-9.  [Content Brief]