Phospho-Mcl-1 (Ser64) Antibody

• 产品编号：CST-13297S      品牌：CST       原厂货号：13297S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Mcl-1 (Ser64)抗体仅可以识别Ser64磷酸化的Mcl-1蛋白。在某些细胞系中会在产生未知来源的70 kDa 和140 kDa 条带。该多抗由合成的Mcl-1蛋白Ser64附近氨基酸对应的肽段免疫动物产生。抗体由蛋白A和肽段亲和层析技术纯化得到。Mcl-1 是Bcl-2抗凋亡家族的成员，在单核细胞/巨噬细胞通路佛波酯诱导分化时，首次从ML-1人髓系白血病细胞系被分离(1) 。类似于其他 Bcl-2 家族成员，Mcl-1定位于线粒体 (2)，与促凋亡Bcl-2 家族成员互作和拮抗（3），抑制细胞毒性刺激诱导的细胞凋亡（4）。与其他家族成员不同，Mcl-1的调控同时涉及了转录和转录后修饰水平。首先，Mcl-1 有一个扩展的氨基末端PEST区域，负责其相对较短的半衰期 (1，2)。第二，与其他家族成员不同，Mcl-1通过PI3K/Akt依赖的通路是迅速被转录，从而在髓细胞分化和细胞因子刺激时表达量增加 (1，5-7)。Mcl-1 在应答佛波酯处理、微管损伤试剂、氧化应激和细胞因子停药时，会被磷酸化(8-11)。磷酸化Thr163，PEST区域内保守的MAP kinase/ERK位点，磷酸化将减慢 Mcl-1 蛋白质转化 (10)，但可能会刺激GSK-3介导的Ser159磷酸化，导致Mcl-的不稳定 (11)。小鼠缺乏Mcl-1会导致围着床期致死(12)。此外，条件性中断相应的 mcl-1 基因显示了Mcl-1在早期淋巴组织发育和维持的成熟淋巴细胞中发挥了重要作用(13)。Mcl-1在Ser64位点的磷酸化，可以使其成为肿瘤抑制蛋白FBW7诱导的泛素化降解的靶点(14,15)。

1. Kozopas, K.M. et al. (1993) Proc Natl Acad Sci USA 90, 3516-20.
2. Yang, T. et al. (1995) J Cell Biol 128, 1173-84.
3. Sato, T. et al. (1994) Proc Natl Acad Sci USA 91, 9238-42.
4. Zhou, P. et al. (1997) Blood 89, 630-43.
5. Wang, J.M. et al. (1999) Mol Cell Biol 19, 6195-206.
6. Jourdan, M. et al. (2003) Oncogene 22, 2950-9.
7. Chao, J.R. et al. (1998) Mol Cell Biol 18, 4883-98.
8. Domina, A.M. et al. (2000) J Biol Chem 275, 21688-94.
9. Inoshita, S. et al. (2002) J Biol Chem 277, 43730-4.
10. Domina, A.M. et al. (2004) Oncogene 23, 5301-15.
11. Maurer, U. et al. (2006) Mol Cell 21, 749-60.
12. Rinkenberger, J.L. et al. (2000) Genes Dev 14, 23-7.
13. Opferman, J.T. et al. (2003) Nature 426, 671-6.
14. Inuzuka, H. et al. (2011) Nature 471, 104-9.
15. Wertz, I.E. et al. (2011) Nature 471, 110-4.

原厂资料：

Specificity / Sensitivity

Phospho-Mcl-1 (Ser64) Antibody recognizes endogenous levels of Mcl-1 protein only when phosphorylated at Ser64. Non-specific bands of unknown origin are detected in some cell lines at 70 and 140 kDa.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser64 of human Mcl-1 protein.

Background

Mcl-1 is an anti-apoptotic member of the Bcl-2 family originally isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway (1). Similar to other Bcl-2 family members, Mcl-1 localizes to the mitochondria (2), interacts with and antagonizes pro-apoptotic Bcl-2 family members (3), and inhibits apoptosis induced by a number of cytotoxic stimuli (4). Mcl-1 differs from its other family members in its regulation at both the transcriptional and post-translational level. First, Mcl-1 has an extended amino-terminal PEST region, which is responsible for its relatively short half-life (1,2). Second, unlike other family members, Mcl-1 is rapidly transcribed via a PI3K/Akt dependent pathway, resulting in its increased expression during myeloid differentiation and cytokine stimulation (1,5-7). Mcl-1 is phosphorylated in response to treatment with phorbol ester, microtubule-damaging agents, oxidative stress, and cytokine withdrawal (8-11). Phosphorylation at Thr163, the conserved MAP kinase/ERK site located within the PEST region, slows Mcl-1 protein turnover (10) but may prime the GSK-3 mediated phosphorylation at Ser159 that leads to Mcl-1 destabilization (11). Mcl-1 deficiency in mice results in peri-implantation lethality (12). In addition, conditional disruption of the corresponding mcl-1 gene shows that Mcl-1 plays an important role in early lymphoid development and in the maintenance of mature lymphocytes (13).Phosphorylation of Mcl-1 at Ser64 can target it for ubiqutination and destruction by the tumor suppressor protein FBW7 (14,15).

1. Kozopas, K.M. et al. (1993) Proc Natl Acad Sci USA 90, 3516-20.
2. Yang, T. et al. (1995) J Cell Biol 128, 1173-84.
3. Sato, T. et al. (1994) Proc Natl Acad Sci USA 91, 9238-42.
4. Zhou, P. et al. (1997) Blood 89, 630-43.
5. Wang, J.M. et al. (1999) Mol Cell Biol 19, 6195-206.
6. Jourdan, M. et al. (2003) Oncogene 22, 2950-9.
7. Chao, J.R. et al. (1998) Mol Cell Biol 18, 4883-98.
8. Domina, A.M. et al. (2000) J Biol Chem 275, 21688-94.
9. Inoshita, S. et al. (2002) J Biol Chem 277, 43730-4.
10. Domina, A.M. et al. (2004) Oncogene 23, 5301-15.
11. Maurer, U. et al. (2006) Mol Cell 21, 749-60.
12. Rinkenberger, J.L. et al. (2000) Genes Dev 14, 23-7.
13. Opferman, J.T. et al. (2003) Nature 426, 671-6.
14. Inuzuka, H. et al. (2011) Nature 471, 104-9.
15. Wertz, I.E. et al. (2011) Nature 471, 110-4.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody