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FK506 结合蛋白作为癌症生物标志物的新作用:以 FKBPL 为例。

The emerging role of FK506-binding proteins as cancer biomarkers: a focus on FKBPL.

机构信息

School of Pharmacy, McClay Research Centre, Queen's University, Belfast, UK.

出版信息

Biochem Soc Trans. 2011 Apr;39(2):663-8. doi: 10.1042/BST0390663.

Abstract

FKBPs (FK506-binding proteins) have long been recognized as key regulators of the response to immunosuppressant drugs and as co-chaperones of steroid receptor complexes. More recently, evidence has emerged suggesting that this diverse protein family may also represent cancer biomarkers owing to their roles in cancer progression and response to treatment. FKBPL (FKBP-like) is a novel FKBP with roles in GR (glucocorticoid receptor), AR (androgen receptor) and ER (oestrogen receptor) signalling. FKBPL binds Hsp90 (heat-shock protein 90) and modulates translocation, transcriptional activation and phosphorylation of these steroid receptors. It has been proposed as a novel prognostic and predictive biomarker, where high levels predict for increased recurrence-free survival in breast cancer patients and enhanced sensitivity to endocrine therapy. Since this protein family has roles in a plethora of signalling pathways, its members represent novel prognostic markers and therapeutic targets for cancer diagnosis and treatment.

摘要

FKBP (FK506 结合蛋白)长期以来一直被认为是免疫抑制剂药物反应的关键调节剂,也是甾体激素受体复合物的共伴侣。最近,有证据表明,由于其在癌症进展和对治疗的反应中的作用,这个多样化的蛋白质家族也可能代表癌症生物标志物。FKBP-L(FKBP 样)是一种新型的 FKBP,在 GR(糖皮质激素受体)、AR(雄激素受体)和 ER(雌激素受体)信号转导中发挥作用。FKBP-L 与 HSP90(热休克蛋白 90)结合,调节这些甾体激素受体的易位、转录激活和磷酸化。它被提议作为一种新的预后和预测生物标志物,高水平预示乳腺癌患者无复发生存率增加,并提高对内分泌治疗的敏感性。由于这个蛋白质家族在众多信号通路中都有作用,其成员是癌症诊断和治疗的新型预后标志物和治疗靶点。

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