Oncotarget

Research Papers:

CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells

Saya Ito, Akihisa Ueno, Takashi Ueda _, Hideo Nakagawa, Hidefumi Taniguchi, Naruhiro Kayukawa, Atsuko Fujihara-Iwata, Fumiya Hongo, Koji Okihara and Osamu Ukimura

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Oncotarget. 2018; 9:17645-17655. https://doi.org/10.18632/oncotarget.24824

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Abstract

Saya Ito1,*, Akihisa Ueno1,*, Takashi Ueda1,2, Hideo Nakagawa1, Hidefumi Taniguchi1, Naruhiro Kayukawa1, Atsuko Fujihara-Iwata1, Fumiya Hongo1, Koji Okihara1 and Osamu Ukimura1

1Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto-City, Kyoto 602-8566, Japan

2Department of Urology, Uji Takeda Hospital, Uji-City, Kyoto 611-0021, Japan

*These authors equally contributed to this work

Correspondence to:

Takashi Ueda, email: [email protected]

Keywords: CNPY2; prostate cancer; AR; MYLIP; protein degradation

Received: September 29, 2017     Accepted: March 01, 2018     Published: April 03, 2018

ABSTRACT

The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination.


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