ROCK-Dependent Phosphorylation of NUP62 Regulates p63 Nuclear Transport and Squamous Cell Carcinoma Proliferation

Hazawa, Masaharu and Lin, De-Chen and Kobayashi, Akiko and Jiang, Yan-Yi and Liang Xu, Liang Xu and Rahmah, Firli Primula Dewi and Shaaban, Mahmoud and Hartono, Hartono and Nakada, Mitsutoshi and Meguro-Horike, Makiko and Horike, Shin-ichi and Koeffler, H Philip and Wong, Richard W (2017) ROCK-Dependent Phosphorylation of NUP62 Regulates p63 Nuclear Transport and Squamous Cell Carcinoma Proliferation. EMBO Reports, 19 (1). pp. 73-88. ISSN 14693178, 1469221X

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Abstract

p63, more specifically its DNp63a 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 main- tain the undifferentiated status is associated with defects in DNp63a nuclear transport. We further find that differentiation- inducible Rho kinase reduces the interaction between NUP62 and DNp63a by phosphorylation of phenylalanine–glycine regions of NUP62, attenuating DNp63a nuclear import. Our results character- ize NUP62 as a gatekeeper for DNp63a and uncover its role in the control of cell fate through regulation of DNp63a nuclear transport in SCC.

Item Type:	Article
Subjects:	FMIPA
Divisions:	FAKULTAS MIPA
Depositing User:	Zainatun
Date Deposited:	24 Jun 2023 01:20
Last Modified:	24 Jun 2023 01:20
URI:	http://eprints.unm.ac.id/id/eprint/31186

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