Protein kinase D1 phosphorylation of KAT7 enhances its protein stability and promotes replication licensing and cell proliferation

Yao Liang; Yuanyuan Su; Chenzhong Xu; Na Zhang; Doudou Liu; Guodong Li; Tanjun Tong; Jun Chen

doi:10.1038/s41420-020-00323-w

Protein kinase D1 phosphorylation of KAT7 enhances its protein stability and promotes replication licensing and cell proliferation

Cell Death Discov. 2020 Sep 18;6(1):89. doi: 10.1038/s41420-020-00323-w. eCollection 2020.

Authors

Yao Liang¹, Yuanyuan Su¹, Chenzhong Xu¹, Na Zhang¹, Doudou Liu¹, Guodong Li¹, Tanjun Tong¹, Jun Chen¹

Affiliation

¹ Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, Beijing, 100191 China.

Abstract

The histone acetyltransferase (HAT) KAT7/HBO1/MYST2 plays a crucial role in the pre-replication complex (pre-RC) formation, DNA replication and cell proliferation via acetylation of histone H4 and H3. In a search for protein kinase D1 (PKD1)-interacting proteins, we have identified KAT7 as a potential PKD1 substrate. We show that PKD1 directly interacts and phosphorylates KAT7 at Thr97 and Thr331 in vitro and in vivo. PKD1-mediated phosphorylation of KAT7 enhances its expression levels and stability by reducing its ubiquitination-mediated degradation. Significantly, the phospho-defective mutant KAT7-Thr97/331A attenuates histone H4 acetylation levels, MCM2/6 loading on the chromatin, DNA replication and cell proliferation. Similarly, PKD1 knockdown decreases, whereas the constitutive active mutant PKD1-CA increases histone H4 acetylation levels and MCM2/6 loading on the chromatin. Overall, these results suggest that PKD1-mediated phosphorylation of KAT7 may be required for pre-RC formation and DNA replication.

Keywords: Chemical modification; Kinases.

Abstract

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