Characterization of pinin, a novel protein associated with the desmosome-intermediate filament complex.

Ouyang, Pin; Sugrue, Stephen P.

doi:10.1083/jcb.135.4.1027

Cited by 83 publications

(63 citation statements)

References 59 publications

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“…Prior in vitro studies demonstrated that PNN overexpression results in the enhanced epithelial phenotype characterized by increased cell-cell adhesion and decreased motility (Ouyang and Sugrue, 1996;Shi et al, 2000bShi et al, , 2001). Down-regulation of PNN by shRNA causes cells to become less adherent and more migratory and leads to down-regulation of several key adhesion molecules, including desmoplakin, ZO-1, and E-cadherin, which is a hallmark of neoplastic transformation (Joo et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Joo

Lee

Munguba

et al. 2007

Developmental Dynamics

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Previous in vitro studies have indicated multiple and varied roles of Pinin (PNN); however, its in vivo role has remained unclear. Here, we report generation of null, hypomorphic, and conditional Pnn alleles in mice. We found that insertion of neomycin-resistance cassette into intron 8 of Pnn resulted in knockdown of Pnn, which allowed Pnn hypomorphic embryos to pass peri-implantation lethality. These mice are lethal at perinatal stages and exhibit defects in the cardiac outflow tract, palate, dorsal dermis, and axial skeleton. Since Wnt/␤-catenin signaling has been shown to play pivotal roles in development of all tissues affected by Pnn hypomorphism, we speculated that Pnn may affect Wnt/␤-catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in ␤-catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pnn plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity. Developmental Dynamics 236: 2147-2158, 2007.

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Section: Introductionmentioning

confidence: 99%

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Joo

Lee

Munguba

et al. 2007

Developmental Dynamics

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“…4). We also isolated pinin, a desmosome-associated protein (48). Although no functional connection between pinin and splicing has been demonstrated, pinin localizes to splicing speckles in both Xenopus spp.…”

Section: Cloning and Analysis Of Murine Prp4k And Its Homologuesmentioning

confidence: 99%

Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes

Dellaire

Makarov

Cowger

et al. 2002

Molecular and Cellular Biology

135

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A growing body of evidence supports the coordination of pre-mRNA processing and transcriptional regulation. We demonstrate here that mammalian PRP4 kinase (PRP4K) is associated with complexes involved in both of these processes. PRP4K is implicated in pre-mRNA splicing as the homologue of the Schizosaccharomyces pombe pre-mRNA splicing kinase Prp4p, and it is enriched in SC35-containing nuclear splicing speckles. RNA interference of Caenorhabditis elegans PRP4K indicates that it is essential in metazoans. In support of a role for PRP4K in pre-mRNA splicing, we identified PRP6, SWAP, and pinin as interacting proteins and demonstrated that PRP4K is a U5 snRNP-associated kinase. In addition, BRG1 and N-CoR, components of nuclear hormone coactivator and corepressor complexes, also interact with PRP4K. PRP4K coimmunoprecipitates with N-CoR, BRG1, pinin, and PRP6, and we present data suggesting that PRP6 and BRG1 are substrates of this kinase. Lastly, PRP4K, BRG1, and PRP6 can be purified as components of the N-CoR-2 complex, and affinity-purified PRP4K/N-CoR complexes exhibit deacetylase activity. We suggest that PRP4K is an essential kinase that, in association with the both U5 snRNP and N-CoR deacetylase complexes, demonstrates a possible coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation.The regulation of eukaryotic gene expression involves the modulation of chromatin structure and the coordinated transcription and splicing of mRNA. Both histone modification (61) and chromatin remodeling modulate the access of the transcriptional apparatus to chromatin (14, 44). The SWI/SNF proteins are the archetypal family of ATPases involved in remodeling chromatin, and members of this family in both yeast (Snf2) and mammals (BRG1) have been isolated in association with the RNA polymerase II holoenzyme complex (45, 59). Once transcription has been initiated it is thought that premRNA splicing occurs cotranscriptionally (4,22). A number of recent studies have also shown links between corepressor and coactivator complexes and pre-mRNA splicing (e.g., PSF [40] and PGC1 [42], respectively), which suggests yet another level of coordination between the regulation of gene expression and pre-mRNA splicing.If chromatin remodeling and pre-mRNA splicing occur in coordination with transcription, there may be proteins that either play a direct role in both chromatin structure and splicing and/or interact with factors involved in each process. Previously, we isolated a murine gene-trap protein, designated CT143 (56), which is similar to Schizosaccharomyces pombe Prp4 kinase (17). Prp4p is essential for pre-mRNA splicing, as demonstrated by the accumulation of unspliced pre-mRNA at the restrictive temperature in yeast carrying a temperaturesensitive (ts) mutation in prp4 (2). Prp4p interacts genetically with other S. pombe splicing proteins, including the non-SR splicing proteins Prp1p (a homologue of Saccharomyces cerevisiae Prp6p) and Prp5p (51). Multiple rounds of phosphorylation and d...

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“…Yeast two-hybrid assay and co-immunoprecipitation experiments demonstrated that Pnn interacts with several splicing-related SR family proteins, including SRp75, SRm300, SRp130, SRcyclophilin and RNPS1 and binds preferentially to splicedmRNA (Li et al, 2003;Lin et al, 2004;Zimowska et al, 2003). Apart from its roles within the nucleus, Pnn has also been shown to be involved in other cellular functions including the enhancement of cell-cell adhesion (Ouyang and Sugrue, 1996) and corneal cell migration (Shi et al, 2000b). Abnormal expression of Pnn in tumor cells has also been reported (Shi et al, 2000a).…”

Section: Introductionmentioning

confidence: 99%

“…Pinin (Pnn), a SR-related protein, was originally characterized as a desmosome-associated protein found at the cytoplasmic face of the desmosome plaque at the convergence of intermediate filaments (Ouyang and Sugrue, 1992;Ouyang and Sugrue, 1996). Subsequent studies have demonstrated that Pnn not only exists at epithelial cell-cell contact sites, but also localizes in the nuclear 'speckle' domain, a subnuclear region for assembly and storage of splicing factors (Brandner et al, 1997;Ouyang, 1999).…”

Section: Introductionmentioning

confidence: 99%

Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICA**

Leu

Lin

et al. 2012

Journal of Cell Science

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SummaryPinin (Pnn), a serine/arginine-rich (SR)-related protein, has been shown to play multiple roles within eukaryotic cells including cell-cell adhesion, cell migration, regulation of gene transcription, mRNA export and alternative splicing. In this study, an attempt to generate mice homozygously deficient in Pnn failed because of early embryonic lethality. To evaluate the effects of loss of Pnn expression on cell survival, RNA interference experiments were performed in MCF-7 cells. Depletion of Pnn resulted in cellular apoptosis and nuclear condensation. In addition, nuclear speckles were disrupted, and expression levels of SR proteins were diminished. RT-PCR analysis showed that alternative splicing patterns of SRSF1 as well as of apoptosis-related genes Bcl-x and ICAD were altered, and expression levels of Bim isoforms were modulated in Pnn-depleted cells. Cellular apoptosis induced by Pnn depletion was rescued by overexpression of SRSF1, which also restored generation of Bcl-xL and functionless ICAD. Pnn expression is, therefore, essential for survival of mouse embryos and the breast carcinoma cell line MCF-7. Moreover, Pnn depletion, modulated by SRSF1, determines cellular apoptosis through activation of the expression of pro-apoptotic Bcl-xS transcripts.

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Characterization of pinin, a novel protein associated with the desmosome-intermediate filament complex.

Abstract: Abstract. We have identified a protein named pinin that is associated with the mature desmosomes of the epithelia (Ouyang, P., and S.P. Sugrue. 1992. J. Cell

Cited by 83 publications

References 59 publications

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes

Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICA**

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