CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin–proteasome

Zhang, Pei Jing; Zhao, Jie; Li, Hui Yan; Man, Jiang Hong; He, Kun; Zhou, Tao; Pan, Xin; Li, Ai Ling; Gong, Wenbin; Jin, Bao Feng; Xia, Qing; Yu, Ming; Shen, Bei Fen; Zhang, Xue Min

doi:10.1038/sj.emboj.7601602

Cited by 70 publications

(60 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data revealed 7 upregulated genes in the ubiquitin-proteasome system, including 3 related to subunits of the proteasome, 3 related to ubiquitin and 1 coding an ubiquitin-protein ligating enzyme UBE3A; this implies that there was abnormal activation of the ubiquitinproteasome system during the process of reproductive system dysfunction due to high intensity exercise training. Previous studies have shown that an activated ubiquitin-proteasome system affects oogenesis by targeted cyclin E (20,21). In our study, we also found that ER and PR were downregulated in the ovaries in the exercise training group rats.…”

Section: Discussionsupporting

confidence: 73%

High intensity training induces alteration of the ubiquitin-proteasome system gene expression profile and structural changes in the ovaries

et al. 2012

View full text Add to dashboard Cite

Abstract. The female reproductive system is highly sensitive to physiological stress. However, the mechanism(s) involved in dysfunction of the ovaries induced by high intensity exercise training remain unknown. In the present study, we established a rat model of high intensity exercise training, and investigated the morphological and functional changes in ovaries. Furthermore, we profiled the differential gene expression in the ovaries between high intensity exercise training rats and control rats by restriction fragment differential display PCR. Differentially expressed genes were validated by real-time PCR. The results showed that the weight and microstructure of the ovaries were significantly altered in the exercise training group rats. In addition, the levels of estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone were significantly decreased in the exercise training group rats compared with the control group rats. Immunohistochemistry revealed weak expression of estradiol, estrogen receptor and progesterone receptor in ovarian tissues from the high intensity exercise training group compared with the control group. Furthermore, the gene expression profiles of the exercise training and control group rats were analyzed, and differentially expressed genes, such as those involved in the ubiquitin-proteasome system, were identified. Our results indicate that high intensity exercise training can suppress the cellular function of the ovary glands. The mechanism may involve a series of alterations in the expression of genes particularly associated with the ubiquitin-proteasome system.

show abstract

Section: Discussionsupporting

confidence: 73%

High intensity training induces alteration of the ubiquitin-proteasome system gene expression profile and structural changes in the ovaries

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Its gene product also activates a variety of viral and cellular promoters in diverse cell types. Although HBX does not bind to dsDNA, it does regulate transcription of a variety of cellular and viral genes by interacting with cellular proteins and/or components of signal transduction pathways (39,40). The interaction of HBX with these proteins leads to activation of signal transduction pathways including Ras/Raf/MAPK, protein kinase C, and Jak1-STAT.…”

Section: Discussionmentioning

confidence: 99%

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Wei¹,

Song

et al. 2010

The Journal of Immunology

204

185

View full text Add to dashboard Cite

show abstract

“…Immunoprecipitation and immunoblotting were performed as described previously (48). To detect p53 acetylation, cells were lysed in lysis buffer [20 mM Tris⅐HCl (pH 8.0), 150 mM NaCl, 0.5% Nonidet P-40, 5 mM MgCl 2, 2 mM EDTA, 1 mM Na3VO4, 5 m⌴ trichostatin A, and protease inhibitor mixture].…”

mentioning

confidence: 99%

“…Cells were transfected by using Lipofectamine 2000 (Invitrogen) following the manufacturer's instructions. Luciferase assays were performed as described previously (48,49).…”

mentioning

confidence: 99%

Induction of SOX4 by DNA damage is critical for p53 stabilization and function

Pan

Zhao²,

Zhang³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

121

113

View full text Add to dashboard Cite

DNA damage response (DDR) acts as a tumorigenesis barrier, and any defects in the DDR machinery may lead to cancer. SOX4 expression is elevated in many types of tumors; however, its role in DDR is still largely unknown. Here, we show that SOX4, a new DNA damage sensor, is required for the activation of p53 tumor suppressor in response to DNA damage. Notably, SOX4 interacts with and stabilizes p53 protein by blocking Mdm2-mediated p53 ubiquitination and degradation. Furthermore, SOX4 enhances p53 acetylation by interacting with p300/CBP and facilitating p300/CBP/p53 complex formation. In concert with these results, SOX4 promotes cell cycle arrest and apoptosis, and it inhibits tumorigenesis in a p53-dependent manner. Therefore, these findings highlight SOX4 as a potential key factor in regulating DDR-associated cancer.Mdm2 ͉ ubiquitination ͉ tumorigenesis D NA damage response (DDR), a highly conserved response to genotoxic stresses, is the guardian of genomic integrity (1, 2). It has been shown that DDR serves as a barrier to constrain tumor progression in its early stages by inducing cell cycle arrest, DNA repair, or apoptosis (3). A number of components are involved in cellular DDR machinery, in which ATM-Chk2-p53 and ATRChk1-p53 cascade are the key signaling pathways involved (2). A central component of DDR, p53, is one of the most important tumor suppressor proteins (4-8). The major consequence of p53 activation upon DNA damage is the induction of specific target genes, such as p21 WAF , Bax, and Puma, to initiate cell cycle arrest, apoptosis, and DNA repair (4). Cells lacking functional p53 exhibit a partial deficiency in DNA damage repair, resulting in uncontrolled cell proliferation and malignancy. Indeed, p53 gene is either lost or mutated in more than half of all human cancers (9). Around p53 there is a highly regulated network consisting of numerous proteins that interact with p53 and regulate its activity by protein stabilization, posttranscriptional modifications, protein-protein interaction, and protein subcellular localization (10), among which stabilization of p53 is presumed to play a major role in its activation. Under normal conditions, amount and activity of p53 are maintained at low levels by Mdm2, a ubiquitin E3 ligase, which binds to the N terminus of p53 and targets its C-terminal lysine residues for ubiquitination and degradation (11,12). However, in response to DNA damage, p53 protein is rapidly stabilized and activated mostly through multiple posttranslational modifications, such as phosphorylation and acetylation of specific residues in the N-terminal and C-terminal domains. DNA damage-induced p53 phosphorylation, which is mediated by ATM kinase (13, 14), contributes to p53 stability (15). Acetylation of p53 C-terminal lysine residues in p53 stabilizes the protein by preventing Mdm2-mediated ubiquitination of the same residues (16,17). In addition, the activity of p53 is also modulated by its recruitment of transcriptional coactivators or corepressors.SOX4 is a member of the SOX (SRY-re...

show abstract

CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin–proteasome

Cited by 70 publications

References 47 publications

High intensity training induces alteration of the ubiquitin-proteasome system gene expression profile and structural changes in the ovaries

High intensity training induces alteration of the ubiquitin-proteasome system gene expression profile and structural changes in the ovaries

The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein

Induction of SOX4 by DNA damage is critical for p53 stabilization and function

Contact Info

Product

Resources

About