Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1: A possible regulation of splicing by a complex formation

Harada, Kenji; Yamada, Akira; Yang, Damu; Itoh, Kyogo; Shichijo, Shigeki

doi:10.1002/ijc.1391

Cited by 27 publications

(27 citation statements)

References 37 publications

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“…It is of considerable interest that the effects of cotransfection of RNPS1-associated factors were not only additive but also synergistic with regards to the regulation of alternative splicing. In a calcitonin/dhfr chimeric pre-mRNA, it was reported that the coexpression of both RNPS1 and SART3 represses the relative use of a distal 3Ј splice site, however, overexpression of either protein alone did not cause significant changes in the alternative 3Ј splice site choice (37). In the hTra2␤ pre-mRNA, overexpression of RNPS1 alone induces alternative doubleexon skipping (beta 3 splicing) and this effect is additive upon coexpression of either hTra2␤ or p54, which cause single-exon (beta 1) or double-exon (beta 3) skipping, respectively.…”

Section: Rnps1-interacting Factorsmentioning

confidence: 99%

“…2B). Previously, the N-terminal region of RNPS1, which includes the S domain, was shown to be necessary for the interaction with PITSLRE p110 kinase and a tumor-rejection antigen, SART3 (37,56).…”

Section: Rnps1-interacting Factors Identified By Yeast Two-hybrid Scrmentioning

confidence: 99%

“…Previously, RNPS1 was identified by two-hybrid screens with the following proteins as bait: the protein kinases, Clk/Sty and PITSLRE p110 (23,56); the tumor-rejection RNA-binding antigen SART3 (37); and pinin (53; P. Ouyang and W. Y. Tarn, unpublished data). However, of these proteins we only detected pinin using RNPS1 as bait.…”

Section: Rnps1-interacting Factorsmentioning

confidence: 99%

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Human RNPS1 and Its Associated Factors: a Versatile Alternative Pre-mRNA Splicing Regulator In Vivo

Sakashita

Tatsumi

Werner

et al. 2004

Molecular and Cellular Biology

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Human RNPS1 was originally purified and characterized as a pre-mRNA splicing activator, and its role in the postsplicing process has also been proposed recently. To search for factors that functionally interact with RNPS1, we performed a yeast two-hybrid screen with a human cDNA library. Four factors were identified: p54 (also called SRp54; a member of the SR protein family), human transformer 2␤ (hTra2␤; an exonic splicing enhancer-binding protein), hLucA (a potential component of U1 snRNP), and pinin (also called DRS and MemA; a protein localized in nuclear speckles). The N-terminal region containing the serine-rich (S) domain, the central RNA recognition motif (RRM), and the C-terminal arginine/serine/proline-rich (RS/P) domain of RNPS1 interact with p54, pinin, and hTra2␤, respectively. Protein-protein binding between RNPS1 and these factors was verified in vitro and in vivo. Overexpression of RNPS1 in HeLa cells induced exon skipping in a model ␤-globin pre-mRNA and a human tra-2␤ pre-mRNA. Coexpression of RNPS1 with p54 cooperatively stimulated exon inclusion in an ATP synthase ␥-subunit pre-mRNA. The RS/P domain and RRM are necessary for the exon-skipping activity, whereas the S domain is important for the cooperative effect with p54. RNPS1 appears to be a versatile factor that regulates alternative splicing of a variety of pre-mRNAs.Most pre-mRNAs in higher eukaryotes complete accurate splicing in the nucleus, as a prerequisite for carrying the correct genetic information to the cytoplasm for translation. Constitutive splicing is highly precise and is sensitive to mutations in critical signal sequences of the pre-mRNA. Indeed, human genetic diseases are often caused by point mutations that lie in 5Ј or 3Ј splice site elements or by creation of new ones at inappropriate locations, which result in splicing defects (reviewed in references 33 and 50). On the other hand, a subset of pre-mRNAs shows sufficient flexibility for alternative potential splice sites to be used, often in a regulated way in response to tissue-specific or developmentally regulated states (reviewed in references 24, 55, and 82). This process, called alternative splicing, is a basic strategy for the regulation of eukaryotic gene expression. An unexpectedly small set of protein-coding genes, at most 30,000 has recently been estimated in the human genome (51, 72, 79). Indeed, a higher prevalence of alternative splicing than earlier estimates is likely responsible for a larger number of, and more complex, protein products (51, 64).Pre-mRNA splicing takes place within a large complex, or spliceosome, which includes the small nuclear ribonucleoprotein particles (snRNPs) U1, U2, U4/U6, and U5, together with a large number of non-snRNP protein factors. Biochemical characterization of the spliceosome, together with genetic studies in fission and budding yeast, predicted that more than 50 proteins are essential for constitutive splicing (reviewed in references 15 and 73). The members of the serine/arginine-rich protein (SR protein) family are wel...

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Section: Rnps1-interacting Factorsmentioning

confidence: 99%

Section: Rnps1-interacting Factors Identified By Yeast Two-hybrid Scrmentioning

confidence: 99%

Section: Rnps1-interacting Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Human RNPS1 and Its Associated Factors: a Versatile Alternative Pre-mRNA Splicing Regulator In Vivo

Sakashita

Tatsumi

Werner

et al. 2004

Molecular and Cellular Biology

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“…DDB1 (DNA damage binding protein 1) connects DCAF1 and DDA1 (DET1 and DDB1 associated 1) to Cul4A (36,68). The fourth UL35-specific interaction identified was with SART3 (squamous cell carcinoma antigen recognized by T cells 3), an RNA binding protein involved in tumor immunology and mRNA splicing (28,63).…”

Section: Identification Of Ul35 and Ul35a Host Protein Interactions Bmentioning

confidence: 99%

Proteomic Profiling of the Human Cytomegalovirus UL35 Gene Products Reveals a Role for UL35 in the DNA Repair Response

Salsman

Jagannathan

Paladino

et al. 2012

J Virol

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Human cytomegalovirus infections involve the extensive modification of host cell pathways, including cell cycle control, the regulation of the DNA damage response, and averting promyelocytic leukemia (PML)-mediated antiviral responses. The UL35 gene from human cytomegalovirus is important for viral gene expression and efficient replication and encodes two proteins, UL35 and UL35a, whose mechanism of action is not well understood. Here, affinity purification coupled with mass spectrometry was used to identify previously unknown human cellular targets of UL35 and UL35a. We demonstrate that both viral proteins interact with the ubiquitin-specific protease USP7, and that UL35 expression can alter USP7 subcellular localization. In addition, UL35 (but not UL35a) was found to associate with three components of the Cul4 DCAF1 E3 ubiquitin ligase complex (DCAF1, DDB1, and DDA1) previously shown to be targeted by the HIV-1 Vpr protein. The coimmunoprecipitation and immunofluorescence microscopy of DCAF1 mutants revealed that the C-terminal region of DCAF1 is required for association with UL35 and mediates the dramatic relocalization of DCAF1 to UL35 nuclear bodies, which also contain conjugated ubiquitin. As previously reported for the Vpr-DCAF1 interaction, UL35 (but not UL35a) expression resulted in the accumulation of cells in the G 2 phase of the cell cycle, which is typical of a DNA damage response, and activated the G 2 checkpoint in a DCAF1-dependent manner. In addition, UL35 (but not UL35a) induced ␥-H2AX and 53BP1 foci, indicating the activation of DNA damage and repair responses. Therefore, the identified interactions suggest that UL35 can contribute to viral replication through the manipulation of host responses.H uman cytomegalovirus (HCMV) is a member of the betaherpesvirus subfamily and consists of an ϳ230-kbp doublestranded DNA genome encased in an icosahedral capsid, surrounded by a proteinaceous matrix (tegument) layer and a host-derived lipid bilayer containing several viral glycoproteins. HCMV can establish both lytic and latent infections in human hosts yet causes little to no adverse effect in healthy adults. However, lytic HCMV replication is associated with significant disease and sometimes death in immunocompromised hosts, typically transplant recipients, neonates, and people with AIDS (16). HCMV encodes more than 200 viral proteins, although many remain poorly or completely uncharacterized (77). The expression of specific viral proteins is temporally controlled during the three general phases of the lytic replication cycle: the immediate-early (IE), early, and late phases (73). In addition, in the pre-IE phase, tegument-derived viral proteins are delivered to the host cell preformed and therefore can act before viral gene expression occurs to manipulate cells in ways that favor lytic replication (38).Herpesvirus infections are associated with the extensive manipulation of host cell processes, including the control of the cell cycle, apoptosis, immune activation, and the DNA damage response (DDR) (...

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“…Tip110 regulates transcription of viral and several host genes and plays an important role in pre-mRNA splicing and spliceosome assembly (7)(8)(9)(10)(11)(12). Tip110 expression is essential for embryonic development (13).…”

mentioning

confidence: 99%

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

Timani

Liu

Fan

et al. 2015

Molecular and Cellular Biology

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bHypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1␣ (HIF-1␣), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1␣. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1␣ was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1␣ in response to hypoxic stress. Hypoxia is the common characteristic of many solid tumors. The adaptation of cells to hypoxia is mediated by hypoxiainducible factor (HIF), a transcription factor, at the molecular level (1). Under normal oxygen conditions (normoxia), HIF-1␣ is hydroxylated, which promotes its binding to the ubiquitin ligase von Hippel-Lindau protein (pVHL), thereby targeting it for ubiquitin-proteasome system (UPS)-mediated degradation. However, under hypoxic conditions, HIF-1␣ becomes less hydroxylated, leading to its rapid accumulation and subsequent activation of hundreds of genes involved in cell survival, as well as genes involved in apoptosis (2). This opposing function of HIF in determining different cell fates is dependent on the physiopathological context and differential binding to other key partners, such as tumor suppressor protein p53.Similarly to HIF-1␣, p53 stability is also regulated by the hypoxic condition. p53 plays a crucial role in response to DNA damage, aberrant cell control, apoptosis, and senescence (3, 4). p53 function is constitutively regulated in different types of tumors under hypoxia by different mechanisms, such as p53 mutation, expression of inhibitors, or unknown host regulatory elements leading to induction of resistance to p53-mediated apoptosis. In normal cells, p53 protein expression is maintained at a low, often undetectable level due to ubiquitin-mediated proteasome degradation (5). Upon exposure to stress, such as oncogenic activation and certain hypoxic situations, p53 becomes stabilized. Consequently, p53 activates genes involved in cell cycle regulation and genes involved in apoptotic events (4).HIV-1 Tat-interacting protein 110 (Tip110), also known as "squamous cell carcinoma antigen recognized by T cells 3" (SA...

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Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1: A possible regulation of splicing by a complex formation

Cited by 27 publications

References 37 publications

Human RNPS1 and Its Associated Factors: a Versatile Alternative Pre-mRNA Splicing Regulator In Vivo

Human RNPS1 and Its Associated Factors: a Versatile Alternative Pre-mRNA Splicing Regulator In Vivo

Proteomic Profiling of the Human Cytomegalovirus UL35 Gene Products Reveals a Role for UL35 in the DNA Repair Response

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

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