Ubiquitin-specific peptidase 3 induces TPA-mediated leukemia cell differentiation via regulating H2AK119ub

Chae, Yun-Cheol; Jung, Hyeonsoo; Kim, Jiyoung; Lee, Dong Hoon; Seo, Sang-Beom

doi:10.1080/19768354.2019.1661283

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…Both over-and under-expression of USP3 have been shown to have effects consistent with tumorigenesis. For example, USP3 promoted proliferation in a number of cancers (Fang et al, 2018;Wu et al, 2019;Das et al, 2020;Li et al, 2020;Liao et al, 2020) while other reports show that depletion of USP3 can increase the incidence of spontaneous tumors (Lancini et al, 2016), promote metastasis (Wang et al, 2017), inhibit leukemia cell differentiation (Chae et al, 2019), and accelerate degradation of TP53 leading to enhanced proliferation and transformation (Fu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

Gažová

Lefèvre

Bush

et al. 2021

Front. Cell Dev. Biol.

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USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.

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Section: Discussionmentioning

confidence: 99%

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

Gažová

Lefèvre

Bush

et al. 2021

Front. Cell Dev. Biol.

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“… Diseases The role of USP3 Related molecule References Breast cancer + KLF5 Wu et al [ 64 ] Colorectal cancer − SMAD4 Wang et al [ 67 ] AR Zheng et al [ 69 ] Esophageal cancer + Aurora A Shi et al [ 62 ] Gallbladder cancer + PKLR Liang et al [ 57 ] Glioblastoma + Snail Fan et al [ 45 ] miR455-5p Chen et al [ 46 ] Smo Tu et al [ 18 ] Gastric cancer + SND1-IT1 Jin et al [ 40 ] COL9A3 COL6A5 Wu et al (2021) miR-224-5p Li et al [ 39 ] SUZ12 Wu et al [ 64 ] / Fang at al. [ 37 ] Human immunodeficiency virus-1 − A3G Zhao et al [ 34 ] Influenza A virus + miR-26a Gao et al [ 31 ] Leukemia − H2AK119ub Chae et al [ 65 ] Neuroblastoma + ALYREF Nagy et al [ 50 ] REST ...…”

Section: Usp3 In Cancersmentioning

confidence: 99%

“…Notably, USP3 individually makes breast cancer cells resistant to drugs [ 64 ]. Interestingly, USP3 may play an integral role in acute myeloid leukemia as a tumor suppressor by regulating H2AK119u in 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced differentiation of HL-60 cells, which offers a prospective therapeutic approach [ 65 ]. Current studies in colorectal cancer (CRC) may be slightly contradictory.…”

Section: In Other Cancersmentioning

confidence: 99%

Ubiquitin specific peptidase 3: an emerging deubiquitinase that regulates physiology and diseases

Wang,

Shi,

Niu

et al. 2024

Cell Death Discov.

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Proteins are the keystone for the execution of various life activities, and the maintenance of protein normalization is crucial for organisms. Ubiquitination, as a post-transcriptional modification, is widely present in organisms, and it relies on the sophisticated ubiquitin-proteasome (UPS) system that controls protein quality and modulates protein lifespan. Deubiquitinases (DUBs) counteract ubiquitination and are essential for the maintenance of homeostasis. Ubiquitin specific peptidase 3 (USP3) is a member of the DUBs that has received increasing attention in recent years. USP3 is a novel chromatin modifier that tightly regulates the DNA damage response (DDR) and maintains genome integrity. Meanwhile, USP3 acts as a key regulator of inflammatory vesicles and sustains the normal operation of the innate immune system. In addition, USP3 is aberrantly expressed in a wide range of cancers, such as gastric cancer, glioblastoma and neuroblastoma, implicating that USP3 could be an effective target for targeted therapies. In this review, we retrace all the current researches of USP3, describe the structure of USP3, elucidate its functions in DNA damage, immune and inflammatory responses and the cell cycle, and summarize the important role of USP3 in multiple cancers and diseases.

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“…Microarray and ChIP-seq data analyses were performed to identify upregulated genes during TPA-induced AML cell differentiation. In AML cells, levels of USP3 are increased after exposure to TPA, resulting in the reduction of H2AK119ub levels [ 91 ]. Thus, USP3 plays an important role in TPA-induced AML cell differentiation by regulating H2AK119ub [ 91 ].…”

Section: Deubiquitination In Amlmentioning

confidence: 99%

“…In AML cells, levels of USP3 are increased after exposure to TPA, resulting in the reduction of H2AK119ub levels [ 91 ]. Thus, USP3 plays an important role in TPA-induced AML cell differentiation by regulating H2AK119ub [ 91 ].…”

Section: Deubiquitination In Amlmentioning

confidence: 99%

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Park

Baek

2022

IJMS

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Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

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Ubiquitin-specific peptidase 3 induces TPA-mediated leukemia cell differentiation via regulating H2AK119ub

Cited by 9 publications

References 18 publications

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

Ubiquitin specific peptidase 3: an emerging deubiquitinase that regulates physiology and diseases

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

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