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  3. Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer

Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer

  • Cell Death Dis. 2022 Aug 17;13(8):717. doi: 10.1038/s41419-022-05165-1.
Dan Zhang  # 1 2,  Jing Tang  # 1 2,  Yunhong Xu  # 1 2,  Xiaoju Huang 1 2,  Yilin Wang 2,  Xin Jin 3 4,  Gang Wu 5 6,  Pian Liu 7 8
Affiliations

Affiliations

  • 1 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. jinxinxy2@csu.edu.cn.
  • 4 Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China. jinxinxy2@csu.edu.cn.
  • 5 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xhzlwg@163.com.
  • 6 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xhzlwg@163.com.
  • 7 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liupianamazing@126.com.
  • 8 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liupianamazing@126.com.
  • # Contributed equally.
PMID: 35977926 DOI: 10.1038/s41419-022-05165-1
Abstract

Lysine crotonylation is a recently discovered post-translation modification involved in transcription regulation, cell signal transduction, and other processes. Scientists have identified several crotonylases and decrotonylases of histones, including P300/CBP, HDACs, and SIRTs. However, the regulation of non-histone protein crotonylation remains unclear. In the current study, we verified that crotonylation was upregulated in hypoxia and promoted liver Cancer cell growth. We performed TMT-labeled quantitative lysine crotonylome analysis in 12 pairs of hepatocellular carcinoma and adjacent liver tissue and identified 3,793 lysine crotonylation sites in 1,428 proteins. We showed that crotonylation of lamin A at the site of K265/270 maintains its subcellular position, promotes liver Cancer cell proliferation, and prevents cellular senescence. Our data indicate that HDAC6 is the decrotonylase of lamin A and downregulated in response to hypoxia, resulting in lamin A K265/270cr. Taken together, our study reveals the lamin A crotonylation in liver Cancer progression and fills the research gap in non-histone protein crotonylation function.

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