Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, 510632, Guangzhou, China.
Cell Death Dis. 2018 May 21;9(6):580. doi: 10.1038/s41419-018-0661-3.
Prohibitin (PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues. Furthermore, studies verified that PHB1 and PHB2 are involved in the biological processes of tumorigenesis, including cancer cell proliferation, apoptosis, and metastasis. Two small molecule inhibitors, Rocaglamide (RocA) and fluorizoline, derived from medicinal plants, were demonstrated to interact directly with PHB1 and thus inhibit the interaction of PHB with Raf-1, impeding Raf-1/ERK signaling cascades and significantly suppressing cancer cell metastasis. In addition, a short peptide ERAP and a natural product xanthohumol were shown to target PHB2 directly and prohibit cancer progression in estrogen-dependent cancers. As more efficient biomarkers and targets are urgently needed for cancer diagnosis and treatment, here we summarize the functional role of prohibitin domain family proteins, focusing on PHB1 and PHB2 in tumorigenesis and cancer development, with the expectation that targeting the prohibitin domain family will offer more clues for cancer therapy.
抑素（PHB）最初是在大鼠肝脏中作为一种抗增殖基因被分离和鉴定的。进化上保守的 PHB 基因编码两种分子量约为 33 kDa 的人蛋白同工型，PHB1 和 PHB2。PHB1 和 PHB2 属于抑素结构域家族，广泛分布于不同的细胞区室，如线粒体、核和细胞膜。大多数研究证实，PHB1 和 PHB2 在癌症与相应正常组织中的表达存在差异。此外，研究证实 PHB1 和 PHB2 参与肿瘤发生的生物学过程，包括癌细胞增殖、凋亡和转移。两种小分子抑制剂，来源于药用植物的 Rocaglamide（RocA）和氟利嗪，被证明可直接与 PHB1 相互作用，从而抑制 PHB 与 Raf-1 的相互作用，阻碍 Raf-1/ERK 信号级联反应，并显著抑制癌细胞转移。此外，短肽 ERAP 和天然产物黄腐醇被证明可直接靶向 PHB2，并抑制雌激素依赖性癌症中的癌症进展。由于癌症诊断和治疗迫切需要更有效的生物标志物和靶点，因此，我们在这里总结抑素结构域家族蛋白的功能作用，重点关注 PHB1 和 PHB2 在肿瘤发生和癌症发展中的作用，期望靶向抑素结构域家族将为癌症治疗提供更多线索。
