Ubiquitin-specific peptidase 3 induces TPA-mediated leukemia cell differentiation via regulating H2AK119ub

Yun-Cheol Chae; Hyeonsoo Jung; Ji-Young Kim; Dong Ho Lee; Sang-Beom Seo

doi:10.1080/19768354.2019.1661283

Ubiquitin-specific peptidase 3 induces TPA-mediated leukemia cell differentiation via regulating H2AK119ub

Anim Cells Syst (Seoul). 2019 Sep 6;23(5):311-317. doi: 10.1080/19768354.2019.1661283. eCollection 2019.

Authors

Yun-Cheol Chae¹, Hyeonsoo Jung¹, Ji-Young Kim¹, Dong Ho Lee¹, Sang-Beom Seo¹

Affiliation

¹ Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, South Korea.

Abstract

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Owing to the chemotherapy associated side effects and toxicity, it is necessary to find a new mechanism, which can identify new potential therapeutic targets at the molecular level. Here, we identified new target genes that are induced during the TPA-induced HL-60 cell differentiation by ChIP-seq and microarray data analysis. Using q-PCR and ChIP assay, we confirmed that the target genes including USP3, USP35, TCF4, and SGK1 are upregulated during TPA-mediated HL-60 cell differentiation. Levels of USP3, one of the deubiquitinating enzymes (DUBs), increased by TPA treatment, resulting in the reduction of H2AK119ub levels. In addition, we revealed that depletion of USP3 inhibits TPA-mediated leukemia cell differentiation q-PCR and FACS analysis. Taken together, our data indicate that USP3 promotes TPA-mediated leukemia cell differentiation via regulating H2AK119ub levels.

Keywords: AML; HL-60 cells; Leukemia cell differentiation; TPA; ubiquitin-specific peptidase 3.

Grants and funding

This research was supported by the Chung-Ang University Research Grants in 2017, National Research Foundation of Korea (NRF) grant and funded by the Ministry of Science ICT and Future Planning (NRF-2019R1A4A2001609).