Methylation of Aurora kinase A by MMSET reduces p53 stability and regulates cell proliferation and apoptosis.

Oncogene
Jin Woo ParkSang-Beom Seo

Abstract

The histone methyltransferase multiple myeloma SET domain protein (MMSET/WHSC1) is highly expressed in diverse tumor types, and its expression appears to be involved in cell proliferation. In this study, we report that MMSET interacts with and methylates Aurora kinase A (AURKA). We show that MMSET-mediated methylation of AURKA induces interaction with p53 as well as enhanced kinase activity of AURKA, which results in the proteasomal degradation of p53. MMSET-mediated p53 degradation increases cell proliferation and results in oncogenic activity. Furthermore, knockdown of MMSET potently inhibits tumorigenic cells and renders them sensitive to growth inhibition by the therapeutic drug, alisertib (AURKA inhibitor). Taken together, our results suggest that MMSET is a regulator of p53 stability via methylation of AURKA in proliferating cells and might be a potential therapeutic target in solid tumors.

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Citations

Jan 9, 2019·Frontiers in Oncology·Eva De SmedtElke De Bruyne
Aug 23, 2020·Communications Biology·Jin Woo ParkSang-Beom Seo
Feb 1, 2020·The Journal of Investigative Dermatology·Yating YinPeisheng Jin
Oct 31, 2021·Reproductive Biology and Endocrinology : RB&E·Peng-Chao WangZeng-Ming Yang

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Methods Mentioned

BETA
pull-down
co-immunoprecipitation
co-IP
ubiquitination
PCR
ChIP
ChIP-seq
FACS
electrophoresis

Software Mentioned

SEQUEST

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