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

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

doi:10.1016/j.bbrc.2022.01.036

Cited by 6 publications

(3 citation statements)

References 22 publications

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“… 139 In colorectal cancer, the oncogenic ubiquitin E3 ligase TRIM25 binds and stabilizes ATAD2 expression following genotoxic stress, which induces a positive ATAD2-E2F-TRIM25 feedback loop whereby ATAD2 acts as a transcriptional co-activator of E2Fs to promote TRIM25 expression. 140 ATAD2 has been shown to act as a chromatin regulator and to play a role in DNA replication during the S phase by enabling the assembly of histone-modifying protein complexes at target gene chromatin loci. 141 , 142 In addition, Duan et al.…”

Section: Genomic Integrity-regulatory Ctasmentioning

confidence: 99%

Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer

Naik,

Lattab,

Qasem

et al. 2024

Molecular Therapy: Oncology

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Section: Genomic Integrity-regulatory Ctasmentioning

confidence: 99%

Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer

Naik,

Lattab,

Qasem

et al. 2024

Molecular Therapy: Oncology

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“…For instance, KDM8 / JMJD5, a histone lysine demethylase/dioxygenase, directly targets ATAD2 to maintain cell survival via AR activation of EZH2 in prostate cancer 19 . Besides, TRIM25 is an oncogenic ubiquitin E3 ligase that feedback regulates ATAD2 expression in a dose-dependent and transcription-independent manner to promote CRC development 61 . Methyltransferase-like 3 (METTL3), a reported m6A “writer”, was found to promote the growth and invasion of osteosarcoma by enhancing the expression of ATAD2, but the regulatory mechanism is unclear 6 .…”

Section: The Molecular Basis Underlying the Regulatory Mechanisms Of ...mentioning

confidence: 99%

ATPase family AAA domain-containing protein 2 (ATAD2): From an epigenetic modulator to cancer therapeutic target

Fu¹,

Zhang²,

Chen³

et al. 2023

Theranostics

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ATPase family AAA domain-containing protein 2 (ATAD2) has been widely reported to be a new emerging oncogene that is closely associated with epigenetic modifications in human cancers. As a coactivator of transcription factors, ATAD2 can participate in epigenetic modifications and regulate the expression of downstream oncogenes or tumor suppressors, which may be supported by the enhancer of zeste homologue 2. Moreover, the dominant structure (AAA + ATPase and bromine domains) can make ATAD2 a potential therapeutic target in cancer, and some relevant small-molecule inhibitors, such as GSK8814 and AZ13824374, have also been discovered. Thus, in this review, we focus on summarizing the structural features and biological functions of ATAD2 from an epigenetic modulator to a cancer therapeutic target, and further discuss the existing small-molecule inhibitors targeting ATAD2 to improve potential cancer therapy. Together, these inspiring findings would shed new light on ATAD2 as a promising druggable target in cancer and provide a clue on the development of candidate anticancer drugs.

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“…As a coactivator of E2Fs, ATAD2 also promotes the expression of oncogenic ubiquitin E3 ligase (TRIM25). TRIM25 can interact with ATAD2 and stabilize its resistance to genotoxic injury, thus forming an ATAD2-E2Fs-TRIM25 positive feedback loop that drives CRC progression [ 34 ]. In addition, ATAD2 is involved in CRND-mediated miR-126-5p/ATAD2 axis.…”

Section: The Role Of Atad2 In Human Malignant Tumorsmentioning

confidence: 99%

Tumor-Promoting ATAD2 and Its Preclinical Challenges

et al. 2022

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ATAD2 has received extensive attention in recent years as one prospective oncogene with tumor-promoting features in many malignancies. ATAD2 is a highly conserved bromodomain family protein that exerts its biological functions by mainly AAA ATPase and bromodomain. ATAD2 acts as an epigenetic decoder and transcription factor or co-activator, which is engaged in cellular activities, such as transcriptional regulation, DNA replication, and protein modification. ATAD2 has been reported to be highly expressed in a variety of human malignancies, including gastrointestinal malignancies, reproductive malignancies, urological malignancies, lung cancer, and other types of malignancies. ATAD2 is involved in the activation of multiple oncogenic signaling pathways and is closely associated with tumorigenesis, progression, chemoresistance, and poor prognosis, but the oncogenic mechanisms vary in different cancer types. Moreover, the direct targeting of ATAD2’s bromodomain may be a very challenging task. In this review, we summarized the role of ATAD2 in various types of malignancies and pointed out the pharmacological direction.

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

Cited by 6 publications

References 22 publications

Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer

Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer

ATPase family AAA domain-containing protein 2 (ATAD2): From an epigenetic modulator to cancer therapeutic target

Tumor-Promoting ATAD2 and Its Preclinical Challenges

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