Characterization of Nuclear Localization Signals (NLSs) and Function of NLSs and Phosphorylation of Serine Residues in Subcellular and Subnuclear Localization of Transformer-2β (Tra2β)

Li, Shujing; Yao, Qi; Zhao, Jingjing; Li, Ya; Liu, Xiaoyan; Chen, Xianhua; Xu, Ping

doi:10.1074/jbc.m113.456715

Cited by 17 publications

(20 citation statements)

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“…, whereas three NLSs were found in mammalian 5-lipoxygenase, human S1-1/RBM10, human Dot1a, and human Tra2␤ (24)(25)(26)(27). As far as we know, there is no reported example of a nuclear protein with more than three NLSs.…”

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confidence: 95%

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

et al. 2014

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confidence: 95%

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

et al. 2014

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“…Furthermore, nuclear import of Tra2␤1 by TRN-SR1 can occur in a phosphorylation-independent manner (32). Structure-function studies indicate that the N-terminal RS domain is necessary for Tra2␤1 localization in nuclear speckles and that phosphorylation promotes cytoplasmic accumulation (31). These findings illustrate that the cytoplasmic-nuclear distribution of Tra2␤1 is regulated differently than that for most SR proteins.…”

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confidence: 60%

“…In this work we address how SRPK1 phosphorylates Tra2␤1, an SRlike protein that contains two RS domains and controls gene splicing in a phosphorylation-dependent manner (10,46). Interestingly, although most SR proteins gain entry into the nucleus through a phosphorylation-dependent process, hyperphosphorylation drives Tra2␤1 into the cytoplasm (30,31), similar to that for the splicing regulator hnRNP1 (47). We show for the first time that SRPK1 directly phosphorylates Tra2␤1, a modification that regulates the alternative splicing of the SMN2 gene.…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have shown that Tra2␤1 hyper-phosphorylation, identified by a gel shift, inhibits RNA binding suggesting a role for kinase-mediated changes in spliceosome assembly and splice-site selection (29). Although SR protein phosphorylation facilitates nuclear entry of SR proteins, hyper-phosphorylated forms of Tra2␤1 are predominantly localized to the cytoplasm in the brain rather than the nucleus (30,31). Furthermore, nuclear import of Tra2␤1 by TRN-SR1 can occur in a phosphorylation-independent manner (32).…”

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confidence: 99%

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Intra-domain Cross-talk Regulates Serine-arginine Protein Kinase 1-dependent Phosphorylation and Splicing Function of Transformer 2β1

Jamros

Aubol

Keshwani

et al. 2015

Journal of Biological Chemistry

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Background: Serine-arginine-rich (SR)-like proteins regulate the alternative splicing of human genes. Results: The serine-arginine protein kinase 1 (SRPK1) phosphorylates transformer 2␤1 (Tra2␤1) at numerous sites regulating RNA binding, splicing of the survival motor neuron 2 gene, and catalytic function of the kinase domain. Conclusion:The two RS domains interact and regulate Tra2␤1 activity in a phosphorylation-dependent manner. Significance: SRPK1 is a regulator of Tra2␤1.

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“…28 Both the RRM region and RS1 are demanded for SFRS10 splicing activity. 27 RRM recognizes and combines with specific RNA sequence to determine splicing specificity and ensure pre-mRNA substrates entering into the splicing pathway, 29 while the RS regions and its phosphorylation status modulate RNA interactions: 23 The phosphorylation of RS1 region decreases RNA binding to RRM, whereas the unphosphorylated RS2 region facilitates the combination. 23 Nevertheless, the shorter protein Tra2b-3 includes a effective RRM sequence but excludes the domain of RS1, and it may serve as a forceful splicing inhibitor resulting from the competitive combination with the same RNA goals.…”

Section: Sfrs10 and Afld A Splicing Factor: Sfrs10mentioning

confidence: 99%

Roles of silent information regulator 1–serine/arginine-rich splicing factor 10–lipin 1 axis in the pathogenesis of alcohol fatty liver disease

Zhou

2017

Exp Biol Med (Maywood)

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Impact statementALD is a major health burden in industrialized countries as well as China. AFLD, the earliest and reversible form of ALD, can progress to hepatitis, fibrosis/cirrhosis, even hepatoma. While the mechanisms, by which ethanol consumption leads to AFLD, are complicated and multiple, and remain incompletely understood. SIRT1, SFRS10, and LIPIN1 had been separately reported to participate in lipid metabolism and the pathogenesis of AFLD. Noteworthy, we found the connection among them via searching articles in PubMed and we had elaborated the connection in detail in this minireview. It seems a new signaling axis, SIRT1-SFRS10-LIPIN1 axis, acting in the pathogenesis of AFLD exists. Further study aimed at SIRT1-SFRS10-LIPIN1 signaling system will possibly offer a more effective therapeutic target for AFLD. AbstractAlcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to alcoholic liver disease (ALD). With the continued ethanol consumption, alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including alcoholic steatohepatitis, fibrosis/cirrhosis, and even eventually progress to hepatocellular carcinoma and liver failure. Furthermore, cell trauma, inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of ethanol-mediated liver lesions. AFLD is characterized by excessive fat deposition in liver induced by excessive drinking, which is related closely to the raised synthesis of fatty acids and triglyceride, reduction of mitochondrial fatty acid b-oxidation, and the aggregation of very-low-density lipoprotein (VLDL). Although little is known about the cellular and molecular mechanisms of AFLD, it seems to be correlated to diverse signal channels. Massive studies have suggested that liver steatosis is closely associated with the inhibition of silent information regulator 1 (SIRT1) and the augment of lipin1 b/a ratio mediated by ethanol. Recently, serine/argininerich splicing factor 10 (SFRS10), a specific molecule functioning in alternative splicing of lipin 1 (LPIN1) pre-mRNAs, has emerged as the central connection between SIRT1 and lipin1 signaling. It seems a new signaling axis, SIRT1-SFRS10-LPIN1 axis, acting in the pathogenesis of AFLD exists. This article aims to further explore the interactions among the above three molecules and their influences on the development of AFLD.

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Characterization of Nuclear Localization Signals (NLSs) and Function of NLSs and Phosphorylation of Serine Residues in Subcellular and Subnuclear Localization of Transformer-2β (Tra2β)

Cited by 17 publications

References 50 publications

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

Intra-domain Cross-talk Regulates Serine-arginine Protein Kinase 1-dependent Phosphorylation and Splicing Function of Transformer 2β1

Roles of silent information regulator 1–serine/arginine-rich splicing factor 10–lipin 1 axis in the pathogenesis of alcohol fatty liver disease

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