TRIM37 controls cancer-specific vulnerability to PLK4 inhibition.

ABSTRACT: Centrosomes catalyse the formation of microtubules needed to assemble the mitotic spindle apparatus¹. Centrosomes themselves duplicate once per cell cycle, in a process that is controlled by the serine/threonine protein kinase PLK4 (refs. ^2,3). When PLK4 is chemically inhibited, cell division proceeds without centrosome duplication, generating centrosome-less cells that exhibit delayed, acentrosomal spindle assembly⁴. Whether PLK4 inhibitors can be leveraged as a treatment for cancer is not yet clear. Here we show that acentrosomal spindle assembly following PLK4 inhibition depends on levels of the centrosomal ubiquitin ligase TRIM37. Low TRIM37 levels accelerate acentrosomal spindle assembly and improve proliferation following PLK4 inhibition, whereas high

SUBMITTER: Meitinger F 

PROVIDER: S-EPMC7501188 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature