TPA-induced cell transformation provokes a complex formation between Pin1 and 90 kDa ribosomal protein S6 kinase 2.

Molecular and Cellular Biochemistry
Young Sik ChoJung-Hyun Shim

Abstract

Post-translational modification of peptidyl cis/trans prolyl isomerase Pin1 is crucial in regulation of gene stability. Pin1 phosphorylation at Ser(16) has been regarded as a marker for Pin1 isomerase activity and introduction of phosphorylation on Ser/Thr-Pro of substrate proteins is prerequisite for its binding activity with Pin1 and subsequent isomerization. Here, we found that 90 kDa ribosomal protein S6 kinase 2 (RSK2) could form a physical complex with Pin1, leading to phosphorylation of Pin1 at Ser(16) ex vivo and in vitro respectively. Intriguingly, Pin1(+/+) mouse embryonic fibroblasts (MEFs) exhibited significantly an increase in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced RSK2 phosphorylation with a marginal Pin1 phosphorylation compared with Pin1(-/-) MEFs. Moreover, TPA-induced Ser(16) Pin1 phosphorylation as well as RSK2 phosphorylation was considerably profound in RSK(+/+) MEFs but not in RSK(-/-) MEFs. Consequently, knockdown of Pin1 using shRNA-Pin1 suppressed TPA-induced cell transformation in JB6 CI41 cells. Overall, these results indicate that Pin1 plays a critical role in TPA-induced tumorigenesis plausibly via physical interaction with RSK2 and reciprocal phosphorylation, therefore suggesting a pote...Continue Reading

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Citations

Aug 16, 2014·Cell Research·Zhimin Lu, Tony Hunter
Jun 4, 2016·Nature Reviews. Cancer·Xiao Zhen Zhou, Kun Ping Lu
Aug 31, 2016·Archives of Pharmacal Research·Sang-Hyun MinKun Ping Lu
Oct 19, 2017·Biological Chemistry·Anja MatenaPeter Bayer
May 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Garam KimHong Seok Choi
Aug 12, 2018·International Journal of Molecular Sciences·Marzia Bianchi, Melania Manco
Aug 31, 2018·Cell Death & Disease·Yang ChenYing-Bin Yang
Mar 21, 2020·Frontiers in Cell and Developmental Biology·Dongmei ChenTae Ho Lee
Mar 16, 2019·Frontiers in Oncology·Alessandro ZanniniGiannino Del Sal
Feb 7, 2019·Frontiers in Pharmacology·Maguie El BoustaniFlavio Rizzolio
Apr 8, 2020·Frontiers in Cell and Developmental Biology·Ji Hoon YuSang-Hyun Min
Apr 4, 2021·Biomedicines·Hsiang-Hao ChuangChih-Jen Yang

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