Tudor Staphylococcal Nuclease (Tudor-SN), a Novel Regulator Facilitating G1/S Phase Transition, Acting as a Co-activator of E2F-1 in Cell Cycle Regulation

Su, Chao; Zhang, Chunyan; Tecle, Adiam; Xue, Fu Shan; He, Jian‐Qing; Song, Juan; Zhang, Wei; Sun, Xiaoming; Ren, Yuanyuan; Silvennoinen, Olli; Yao, Zhi; Yang, Xi; Wei, Minxin; Yang, Jie

doi:10.1074/jbc.m114.625046

Cited by 50 publications

(55 citation statements)

References 32 publications

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“…We also reported earlier that SND1 can form a loop with SMAD family members and reciprocally regulate the promotion of breast cancer metastasis through a TGF-b-signaling pathway (17)(18)(19). As a multifunctional protein, it is likely that SND1 regulates diverse signal pathways involved in proliferation and metastasis in different cancers (20,21).…”

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confidence: 59%

SND1 acts upstream of SLUG to regulate the epithelial–mesenchymal transition (EMT) in SKOV3 cells

et al. 2018

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Staphylococcal nuclease domain‐containing protein 1 (SND1) has been reported as an oncoprotein in a variety of cancers involving multiple processes, including proliferation, angiogenesis, and metastasis. However, the mechanisms underlying metastasis remain largely unknown. Herein, by using the ovarian cancer cell line SKOV3, which has high metastasis ability, we showed that loss‐of‐function of SND1 dramatically suppressed the invasion and migration of SKOV3 cells. We then performed gene expression profiles and further verified (by use of quantitative PCR and Western blot analysis) that loss‐of‐function of SND1 resulted in up‐regulation of epithelial markers, such as epithelial cadherin and claudin 1, and down‐regulation of mesenchymal markers, including neural cadherin and vimentin. Moreover, we illustrated that SLUG, a key transcription factor implicated in epithelial–mesenchymal transition and metastasis, acts as an essential effector of the SND1‐promoted epithelial–mesenchymal transition process via regulating N‐CAD and VIM expression (or E‐CAD and CLDN1). The underlying molecular mechanisms illustrated that SND1 regulates the gene transcriptional activation of SLUG by increasing chromatin accessibility through the recruitment of the acetyltransferases GCN5 and CBP/p300 to the SLUG promoter proximal region. Overall, SND1 was identified as a novel upstream regulator of SLUG, which plays important roles in regulating the E‐CAD/N‐CAD expression switch.—Xin, L., Zhao, R., Lei, J., Song, J., Yu, L., Gao, R., Ha, C., Ren, Y., Liu, X., Liu, Y., Yao, Z., Yang, J. SND1 acts upstream of SLUG to regulate the epithelial‐mesenchymal transition (EMT) in SKOV3 cells. FASEB J. 33, 3795–3806 (2019). http://www.fasebj.org

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confidence: 59%

SND1 acts upstream of SLUG to regulate the epithelial–mesenchymal transition (EMT) in SKOV3 cells

et al. 2018

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“…It functions as a co-activator for the transcription factor E2F-1 facilitating G1/S phase transition [28] . SND1 induces the E3 ubiquitin ligase Smurf1 resulting in ubiquitination and degradation of RhoA and promotion of invasion, migration and metastasis [17] .…”

Section: Downstream Regulators and Oncogenic Mechanismsmentioning

confidence: 99%

The multifaceted oncogene SND1 in cancer: focus on hepatocellular carcinoma

Chidambaranathan-Reghupaty

Mendoza

Fisher

et al. 2018

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Staphylococcal nuclease and tudor domain containing 1 (SND1) is a protein that regulates a complex array of functions. It controls gene expression through transcriptional activation, mRNA degradation, mRNA stabilization, ubiquitination and alternative splicing. More than two decades of research has accumulated evidence of the role of SND1 as an oncogene in various cancers. It is a promoter of cancer hallmarks like proliferation, invasion, migration, angiogenesis and metastasis. In addition to these functions, it has a role in lipid metabolism, inflammation and stress response. The participation of SND1 in such varied functions makes it distinct from most oncogenes that are relatively more focused in their role. This becomes important in the case of hepatocellular carcinoma (HCC) since in addition to typical cancer drivers, factors like lipid metabolism deregulation and chronic inflammation can predispose hepatocytes to HCC. The objective of this review is to provide a summary of the current knowledge available on SND1, specifically in relation to HCC and to shed light on its prospect as a therapeutic target.

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“…Tudor-staphylococcal nuclease (SN), also known as staphylococcal nuclease domain containing 1 (Snd1), is a highly conserved and ubiquitously expressed multifunctional protein (15)(16)(17)(18)(19)(20)(21)(22)(23). This enzyme comprises a tandem repeat of 4 SN-like domains (referred to as SN domains) at the N terminus and a fusion of a Tudor domain with a partial SN domain at the C terminus (referred to as a TSN domain) (22).…”

mentioning

confidence: 99%

“…This protein plays important roles in the early stage of the DNA damage response in a poly-ADP-ribosylation-dependent manner via interaction with poly (ADP-ribose) polymerase (Parp)-1 through an SN domain (23). Tudor-SN, which is indispensable for normal development, promotes cell-cycle progression by facilitating E2F-1-mediated gene transcription (17). Owing to a high protein-protein binding affinity coexisting with enzymatic activity, Tudor-SN can exert its biochemical function by acting as a scaffolding molecule for large multiprotein complexes, as a nuclease, or both (22).…”

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confidence: 99%

Global Tudor‐SN transgenic mice are protected from obesity‐induced hepatic steatosis and insulin resistance

et al. 2018

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In the current study, we explored the impact of Tudor‐staphylococcal nuclease (SN) on obesity induced by a high‐fat diet (HFD) in mice, because the functional involvement of Tudor‐SN in lipid metabolism in vivo is unknown. HFD‐transgenic (Tg) mice exhibited reductions in hepatic steatosis and systemic insulin resistance. There was no difference in hepatic lipid accumulation between chow‐fed wild‐type (WT) and chow‐fed Tg mice; consistently, no difference in activation of the lipogenic pathway was detected. Overactivation of hepatic nuclear sterol regulatory element‐binding protein (nSrebp2)‐2, the central regulator of cholesterol metabolic proteins, was observed in HFD‐Tg livers along with improved cholesterol homeostasis, but no such changes were observed in HFD‐WT livers. Consistent results were observed in vitro in α‐mouse liver 12 cells treated with palmitate mimicking the HFD state. In addition, global gene analysis indicated that various downstream targets of nSrebp2, were up‐regulated in HFD‐Tg livers. Moreover, HFD‐WT mice displayed islet hypertrophy and suppression of glucose‐induced insulin secretion from islets, whereas HFD‐Tg mice had normal pancreatic islets. This finding suggests that the improved pancreatic metabolism of HFD‐Tg mice is related to the systemic effect of insulin resistance, not to the autonomous influence of pancreatic cells. Tudor‐SN is likely to be a key regulator for ameliorating HFD‐induced hepatic steatosis and systemic insulin resistance in vivo.—Wang, X., Xin, L., Duan, Z., Zuo, Z., Wang, Y., Ren, Y., Zhang, W., Sun, X., Liu, X., Ge, L., Yang, X., Yao, Z., Yang, J. Global Tudor‐SN transgenic mice are protected from obesity‐induced hepatic steatosis and insulin resistance. FASEB J. 33, 3731–3745 (2019). http://www.fasebj.org

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Tudor Staphylococcal Nuclease (Tudor-SN), a Novel Regulator Facilitating G1/S Phase Transition, Acting as a Co-activator of E2F-1 in Cell Cycle Regulation

Cited by 50 publications

References 32 publications

SND1 acts upstream of SLUG to regulate the epithelial–mesenchymal transition (EMT) in SKOV3 cells

SND1 acts upstream of SLUG to regulate the epithelial–mesenchymal transition (EMT) in SKOV3 cells

The multifaceted oncogene SND1 in cancer: focus on hepatocellular carcinoma

Global Tudor‐SN transgenic mice are protected from obesity‐induced hepatic steatosis and insulin resistance

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