scispace - formally typeset
Search or ask a question
Author

Yong Sam Jung

Bio: Yong Sam Jung is an academic researcher from University of California, Davis. The author has contributed to research in topics: Gene knockdown & Regulation of gene expression. The author has an hindex of 20, co-authored 25 publications receiving 1092 citations. Previous affiliations of Yong Sam Jung include Nanjing Agricultural University & Chungnam National University.

Papers
More filters
Journal ArticleDOI
TL;DR: The activity of p21 is discussed and current knowledge of the determinants that control p21 transcription, mRNA stability and translation, and protein stability and activity are focused on.

373 citations

Journal ArticleDOI
TL;DR: It is concluded that FDXR and p53 are mutually regulated and that theFDXR-p53 loop is critical for tumor suppression via iron homeostasis.
Abstract: Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had a short life span and were prone to spontaneous tumors and liver abnormalities, including steatosis, hepatitis, and hepatocellular carcinoma. We also found that FDXR was necessary for mitochondrial iron homeostasis and proper expression of several master regulators of iron metabolism, including iron regulatory protein 2 (IRP2). Surprisingly, we found that p53 mRNA translation was suppressed by FDXR deficiency via IRP2. Moreover, we found that the signal from FDXR to iron homeostasis and the p53 pathway was transduced by ferredoxin 2, a substrate of FDXR. Finally, we found that p53 played a role in iron homeostasis and was required for FDXR-mediated iron metabolism. Together, we conclude that FDXR and p53 are mutually regulated and that the FDXR-p53 loop is critical for tumor suppression via iron homeostasis.

82 citations

Journal ArticleDOI
TL;DR: In vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and its role as a tumor suppressor are revealed and low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival.
Abstract: Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2−/− mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor.

68 citations

Journal ArticleDOI
TL;DR: PolH, a target of the p53 tumor suppressor, is a short-half-life protein that is degraded by proteasome, which is enhanced upon UV irradiation and observed that Pirh2 knockdown leads to accumulation of PolH and, subsequently, enhances the survival of UV-irradiated cells.
Abstract: DNA polymerase eta (PolH), a Y family translesion polymerase, is required for repairing UV-induced DNA damage, and loss of PolH is responsible for early onset of malignant skin cancers in patients with xeroderma pigmentosum variant (XPV), an autosomal recessive disorder. Here, we show that PolH, a target of the p53 tumor suppressor, is a short-half-life protein. We found that PolH is degraded by proteasome, which is enhanced upon UV irradiation. We also found that PolH interacts with Pirh2 E3 ligase, another target of the p53 tumor suppressor, via the polymerase-associated domain in PolH and the RING finger domain in Pirh2. In addition, we show that overexpression of Pirh2 decreases PolH protein stability, whereas knockdown of Pirh2 increases it. Interestingly, we found that PolH is recruited by Pirh2 and degraded by 20S proteasome in a ubiquitin-independent manner. Finally, we observed that Pirh2 knockdown leads to accumulation of PolH and, subsequently, enhances the survival of UV-irradiated cells. We postulate that UV irradiation promotes cancer formation in part by destabilizing PolH via Pirh2-mediated 20S proteasomal degradation.

59 citations

Journal ArticleDOI
TL;DR: The mutual regulation between p73 and RNPC1 constitutes a novel feed-forward loop, which might be explored as a target for tumors without a functional p53.
Abstract: p73, a p53 family tumor suppressor, is expressed as TA and ΔN isoforms. Due to the role of p73 in tumor suppression and neural development, its expression and activity are tightly regulated by multiple mechanisms, including transcription and posttranslational modifications. Here, we found that p73 mRNA stability is regulated by RNPC1, an RNA binding protein and a target of the p53 family. We also showed that a CU-rich element in the 3′ untranslated region of p73 is recognized by and responsive to RNPC1. To explore the physiological significance of RNPC1-regulated p73 expression, we showed that the loss of RNPC1 in p53-null mouse embryonic fibroblasts leads to reduced expression of p73, along with decreased expression of p21, p130, and γ-H2A.X, and consequently a decreased number of senescent cells. Furthermore, we observed that knockdown of TAp73 or p21, another target of RNPC1, attenuates the inhibitory effect of RNPC1 on cell proliferation and premature senescence, whereas combined knockdown of TAp73 and p21 completely abolishes it. Due to the fact that RNPC1 is a target of p73, the mutual regulation between p73 and RNPC1 constitutes a novel feed-forward loop, which might be explored as a target for tumors without a functional p53.

54 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: The molecular regulators of senescence phenotypes and how they are used for identifying senescent cells in vitro and in vivo are described and the importance that these levels of regulations have in the development of therapeutic targets is highlighted.

1,218 citations

Journal ArticleDOI
TL;DR: In this paper, the key molecular mechanisms of ferroptosis, including crosstalk with tumour-associated signalling pathways, and discuss potential therapeutic applications of the process are presented.
Abstract: The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy. Ferroptosis is an iron-dependent form of regulated cell death driven by excessive lipid peroxidation. Pharmacological agents, ionizing radiation and cytokines can induce ferroptosis and thus suppress tumour growth, but ferroptosis can also trigger inflammation-associated immunosuppression. The authors describe the key molecular mechanisms of ferroptosis, including crosstalk with tumour-associated signalling pathways, and discuss potential therapeutic applications of ferroptosis.

793 citations

Journal ArticleDOI
TL;DR: This review will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.

711 citations

Journal ArticleDOI
TL;DR: This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence, and highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies.
Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins (RBPs) that contribute to multiple aspects of nucleic acid metabolism including alternative splicing, mRNA stabilization, and transcriptional and translational regulation Many hnRNPs share general features, but differ in domain composition and functional properties This review will discuss the current knowledge about the different hnRNP family members, focusing on their structural and functional divergence Additionally, we will highlight their involvement in neurodegenerative diseases and cancer, and the potential to develop RNA-based therapies

664 citations

Journal ArticleDOI
TL;DR: The past 15 years have seen an explosion in understanding of how cells replicate damaged DNA and how this can lead to mutagenesis, and the Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis.
Abstract: The past 15 years have seen an explosion in our understanding of how cells replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis. This family of polymerases has unique features that enable them to synthesize DNA past damaged bases. However, as they exhibit low fidelity when copying undamaged DNA, it is essential that they are only called into play when they are absolutely required. Several layers of regulation ensure that this is achieved.

598 citations