ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation.

ABSTRACT: p63, more specifically its ?Np63? isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs. Depletion of NUP62 inhibits proliferation and augments differentiation of SCC cells. The impaired ability to maintain the undifferentiated status is associated with defects in ?Np63? nuclear transport. We further find that differentiation-inducible Rho kinase reduces the interaction between NUP62 and ?Np63? by phosphorylation of phenylalanine-glycine regions of NUP62, attenuating ?Np63? nuclear import. Our results characterize NUP62 as a gatekeeper for ?Np63? and uncover its role in the control of cell fate through regulation of ?Np63? nuclear transport in SCC.

SUBMITTER: Hazawa M 

PROVIDER: S-EPMC5757218 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature