别名 PLK-4、PLK4、polo like kinase 4 + [8] |
简介 Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). |
靶点 |
作用机制 PLK4抑制剂 |
最高研发阶段临床1/2期 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
靶点 |
作用机制 PLK4抑制剂 |
非在研适应症- |
最高研发阶段临床1期 |
首次获批国家/地区- |
首次获批日期1800-01-20 |
开始日期2024-02-14 |
申办/合作机构 |
开始日期2021-04-16 |
申办/合作机构 |
开始日期2020-08-10 |
申办/合作机构 |