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. 2023 Oct 7;40(11):325.
doi: 10.1007/s12032-023-02196-2.

HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285

Ziwei Zhou  1 , Liang Zhong  2 , Xuan Chu  1 , Peng Wan  1 , Wenran Dan  1 , Xin Shao  1 , Shuyu Chen  1 , Zhonghui Zhang  1 , Yang Lu  1 , Beizhong Liu  3   4
Affiliations

HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285

Ziwei Zhou et al. Med Oncol. .

Abstract

Cytarabine-resistant acute myeloid leukemia (AML) is a common phenomenon, necessitating the search for new chemotherapeutics. WEE1 participates in cell cycle checkpoint signaling and inhibitors targeting WEE1 (WEE1i) constitute a potential novel strategy for AML treatment. HDAC (histone deacetylase) inhibitors have been shown to enhance the anti-tumor effects of WEE1i but molecular mechanisms of HDAC remain poorly characterized. In this study, the WEE1 inhibitor PD0166285 showed a relatively good anti-leukemia effect. Notably, PD0166285 can arise the expression of HDAC11 which was negatively correlated with survival of AML patients. Moreover, HDAC11 can reduced the anti-tumor effect of PD0166285 through an effect on p53 stability and the changes in phosphorylation levels of MAPK pathways. Overall, the cell cycle inhibitor, PD0166285, is a potential chemotherapeutic drug for AML. These fundings contribute to a functional understanding of HDAC11 in AML.

Keywords: Ac-p53; Acute myeloid leukemia; HDAC11; Ubiquitination; WEE1 inhibitor.

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