TY - JOUR
T1 - ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation
AU - Hazawa, Masaharu
AU - Lin, De Chen
AU - Kobayashi, Akiko
AU - Jiang, Yan Yi
AU - Xu, Liang
AU - Dewi, Firli Rahmah Primula
AU - Mohamed, Mahmoud Shaaban
AU - Hartono,
AU - Nakada, Mitsutoshi
AU - Meguro-Horike, Makiko
AU - Horike, Shin Ichi
AU - Koeffler, H. Phillip
AU - Wong, Richard W.
N1 - Funding Information:
We thank Takayuki Dowaki, Kie Sakai, and Ryota Tsukahara for technical support. This work was funded by an Infiniti Grant and in part by Grants-in-Aid for scientific research (JSPS KAKENHI Grant Number 17K16332) and (JSPS KAKENHI Grant Number 80292423) from the Japan Society for Promotion of Science. This research was supported by the grant provided by The Ichiro Kanehara Foundation. This work was also supported by World Premier International Research Center Initiative (WPI), MEXT, Japan.
Publisher Copyright:
© 2017 The Authors
PY - 2018
Y1 - 2018
N2 - p63, more specifically its ΔNp63α 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 ΔNp63α nuclear transport. We further find that differentiation-inducible Rho kinase reduces the interaction between NUP62 and ΔNp63α by phosphorylation of phenylalanine–glycine regions of NUP62, attenuating ΔNp63α nuclear import. Our results characterize NUP62 as a gatekeeper for ΔNp63α and uncover its role in the control of cell fate through regulation of ΔNp63α nuclear transport in SCC.
AB - p63, more specifically its ΔNp63α 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 ΔNp63α nuclear transport. We further find that differentiation-inducible Rho kinase reduces the interaction between NUP62 and ΔNp63α by phosphorylation of phenylalanine–glycine regions of NUP62, attenuating ΔNp63α nuclear import. Our results characterize NUP62 as a gatekeeper for ΔNp63α and uncover its role in the control of cell fate through regulation of ΔNp63α nuclear transport in SCC.
UR - http://www.scopus.com/inward/record.url?scp=85041864476&partnerID=8YFLogxK
U2 - 10.15252/embr.201744523
DO - 10.15252/embr.201744523
M3 - Article
C2 - 29217659
AN - SCOPUS:85041864476
SN - 1469-221X
VL - 19
SP - 73
EP - 88
JO - EMBO Reports
JF - EMBO Reports
IS - 1
ER -