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

作者全名："Zhou, Ziwei; Zhong, Liang; Chu, Xuan; Wan, Peng; Dan, Wenran; Shao, Xin; Chen, Shuyu; Zhang, Zhonghui; Lu, Yang; Liu, Beizhong"

作者地址："[Zhou, Ziwei; Chu, Xuan; Wan, Peng; Dan, Wenran; Shao, Xin; Chen, Shuyu; Zhang, Zhonghui; Lu, Yang; Liu, Beizhong] Chongqing Med Univ, Cent Lab, Yongchuan Hosp, Chongqing 402160, Peoples R China; [Zhong, Liang; Liu, Beizhong] Chongqing Med Univ, Dept Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Liu, BZ (通讯作者)，Chongqing Med Univ, Cent Lab, Yongchuan Hosp, Chongqing 402160, Peoples R China.; Liu, BZ (通讯作者)，Chongqing Med Univ, Dept Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China."

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001076190400001

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：40

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：Acute myeloid leukemia; WEE1 inhibitor; HDAC11; Ac-p53; Ubiquitination

摘要："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."

基金机构：We also thank the UCSC Xena database for the contribution in our study.

基金资助正文：We also thank the UCSC Xena database for the contribution in our study.