ATAD2 drives colorectal cancer progression by regulating TRIM25 expression via a positive feedback loop with E2F transcriptional factors

Yalin Tong; Jinbei Li; Mengle Peng; Qilan Qian; Wen Shi; Zefeng Chen; Bin Liu

doi:10.1016/j.bbrc.2022.01.036

ATAD2 drives colorectal cancer progression by regulating TRIM25 expression via a positive feedback loop with E2F transcriptional factors

Biochem Biophys Res Commun. 2022 Feb 26:594:146-152. doi: 10.1016/j.bbrc.2022.01.036. Epub 2022 Jan 13.

Authors

Yalin Tong¹, Jinbei Li², Mengle Peng³, Qilan Qian⁴, Wen Shi⁴, Zefeng Chen⁴, Bin Liu⁵

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: fcctongyl@zzu.edu.cn.
² Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, Henan, China.
³ Department of Clinical Laboratory, Henan Provincial Third People's Hospital, Zhengzhou, 450006, Henan, China.
⁴ Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
⁵ Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address: liubin@jou.edu.cn.

PMID: 35085891
DOI: 10.1016/j.bbrc.2022.01.036

Abstract

ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of cancer types, and acts as a co-activator of androgen and estrogen receptors, as well as MYC and E2F transcription factors, to promote tumor cell proliferation. However, the regulation of ATAD2 and its related mechanisms are still elusive. Here, we show that ATAD2 protein was stabilized during DNA damage response in colorectal cancer (CRC) cells. TRIM25, an oncogenic ubiquitin E3 ligase, can interact with ATAD2 and stabilize ATAD2 upon genotoxic insult. We further demonstrated that ATAD2 played a tumor promoting role in CRC and acted as a transcriptional co-activator of E2Fs to promote the expression of TRIM25. Thus, our results revealed an unknown ATAD2-E2Fs-TRIM25 positive feedback loop that drove CRC progression.

Keywords: ATAD2; Colorectal cancer; TRIM25; Ubiquitination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATPases Associated with Diverse Cellular Activities / metabolism*
Animals
Cell Proliferation
Colorectal Neoplasms / metabolism*
DNA-Binding Proteins / metabolism*
Disease Progression
E2F Transcription Factors / metabolism*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Male
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Oligonucleotide Array Sequence Analysis
Proteasome Endopeptidase Complex / metabolism
RNA Interference
Transcription Factors / metabolism*
Tripartite Motif Proteins / metabolism*
Ubiquitin / metabolism*
Ubiquitin-Protein Ligases / metabolism*

Substances

DNA-Binding Proteins
E2F Transcription Factors
Transcription Factors
Trim25 protein, mouse
Tripartite Motif Proteins
Ubiquitin
TRIM25 protein, human
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
ATAD2 protein, human
ATAD2 protein, mouse
ATPases Associated with Diverse Cellular Activities