Zili Inhibits Transforming Growth Factor-β Signaling by Interacting with Smad4

Sun, Huaqin; Li, Dan; Chen, Shu; Liu, Yanyan; Liao, Xinyang; Deng, Wenqian; Li, Na; Zeng, Mei; Tao, Dachang; Ma, Yongxin

doi:10.1074/jbc.m109.079533

Cited by 32 publications

(35 citation statements)

References 33 publications

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“…he PIWI proteins are widely distributed among different animals and have been implicated in functions related to stemcell self-renewal, gametogenesis, epigenetic modulation, transposon control, and embryogenesis (1)(2)(3)(4)(5)(6)(7)(8). The human PIWI family is comprised of four different members, Piwil1/Hiwi, Piwil2/Hili, Piwil3, and Piwil4/Hiwi2 (9).…”

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confidence: 99%

Piwil2 Inhibits Keratin 8 Degradation through Promoting p38-Induced Phosphorylation To Resist Fas-Mediated Apoptosis

Jiang

Zhao

et al. 2014

Molecular and Cellular Biology

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bThe piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells from apoptosis induced by a variety of stress stimuli. However, the role of Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that Piwil2 inhibits Fasmediated apoptosis. By a bacterial two-hybrid screening, we identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate filament protein protecting the cell from Fas-mediated apoptosis. Our results show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein level at the membrane. In addition to our previous finding that Piwil2 inhibits the expression of p53 through the Src/ STAT3 pathway, here we demonstrate that Piwil2 represses p53 phosphorylation through p38. Our present study indicates that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of Piwil2 in apoptosis, and supports that Piwil2 plays an active role in tumorigenesis.

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Piwil2 Inhibits Keratin 8 Degradation through Promoting p38-Induced Phosphorylation To Resist Fas-Mediated Apoptosis

Jiang

Zhao

et al. 2014

Molecular and Cellular Biology

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“…Piwil2-MO was identical to zili-MO1 that was reported previously (Sun et al 2010). The morpholino or mRNAs was microinjected into the yolk or cytoplasm between one-and two-cell stages.…”

Section: Microinjection and Whole-mount In Situ Hybridizationmentioning

confidence: 98%

“…In our previous experiments we found that piwil2 restricted the mesodermal marker shh (sonic hedgehog a) and snail1 at 24 hpf (Sun et al 2010). The effect of piwil2 was contrary to that in mesoderm at bud stage, in which piwil2 positively regulates ntl expression (Figs.…”

Section: Piwil2 Functions To Inhibit Mesodermal Marker Ntl At 24 Hpf mentioning

confidence: 99%

“…In the previous research, we showed that zebrafish expresses piwil2 not only in primordial germ cells (PGCs) but also in axis during early embryogenesis. We have also presented that Piwil2 suppresses Nodal and bone morphogenetic protein (BMP) signals by physically associating with Smad4 and preventing the formation of Smad2/3/4 and Smad1/5/9/4 complex respectively during early embryo development in zebrafish (Sun et al 2010). Fgf signaling is known to play a key role in the induction of the mesoderm and, like Nodal, its role in mesoderm induction appears to be conserved in vertebrates (Zhao et al 2003).…”

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confidence: 99%

“…Zebrafish Piwi2 contains a 3138-bp open reading frame and encodes a putative protein of 1046 amino acids (Sun et al 2010). In the previous research, we showed that zebrafish expresses piwil2 not only in primordial germ cells (PGCs) but also in axis during early embryogenesis.…”

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Piwi-Like 2 Mediates Fibroblast Growth Factor Signaling during Gastrulation of Zebrafish Embryo

Zhao

Sun

Deng

et al. 2010

Tohoku J. Exp. Med.

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Piwi (P-element-induced wimpy testis) proteins have been shown to play important roles in maintenance of germ line stem cells, germ cell proliferation and differentiation, and control of Piwi-interacting RNAs (PiRNAs). PiRNAs comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Fibroblast growth factor (Fgf) signals, mediated partly by no tail gene (ntl ), are responsible for patterning embryo and mesoderm formation. To understand the function of Piwi proteins, we used zebrafish as a model system. In zebrafish, piwi-like 2 gene (piwil2 ) is also required for germ cell differentiation and meiosis. Here we report that piwil2 knockdown is able to inhibit the expression of fibroblast growth factor 8a (fgf8a ). In contrast, injection with piwil2 mRNA enhances fgf8a expression. Knockdown of piwil2 reduces the inductive effect of fgf8a on dorsalized phenotype, in which embryos extend to an oval shape at the end of epiboly stage. Coinjection with fgf8a and piwil2 mRNAs led to more seriously dorsalized phenotype than coinjection with fgf8a mRNA and piwil2 -cMO. In addition, knockdown of piwil2 inhibits the inductive effect of fgf8a on ntl , whereas overexpression of piwil2 enhances the inductive effect of fgf8a on ntl . We also demonstrate that piwil2 positively regulates ntl expression at bud stage, while piwil2 negatively regulates ntl expression at 24 hours post-fertilization. Thus, the functional consequences of piwil2 expression vary during early development of zebrafish embryo. Taken together, we suggest that zebrafish piwil2 is a mediator of Fgf signals in gastrula period.

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Untangling the web: The diverse functions of the PIWI/piRNA pathway

Mani

Juliano

2013

Molecular Reproduction Devel

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SUMMARY Small RNAs impact several cellular processes through gene regulation. Argonaute proteins bind small RNAs to form effector complexes that control transcriptional and post-transcriptional gene expression. PIWI proteins belong to the Argonaute protein family, and bind PIWI-interacting RNAs (piRNAs). They are highly abundant in the germline, but are also expressed in some somatic tissues. The PIWI/piRNA pathway has a role in transposon repression in Drosophila, which occurs both by epigenetic regulation and post-transcriptional degradation of transposon mRNAs. These functions are conserved, but clear differences in the extent and mechanism of transposon repression exist between species. Mutations in piwi genes lead to the upregulation of transposon mRNAs. It is hypothesized that this increased transposon mobilization leads to genomic instability and thus sterility, although no causal link has been established between transposon upregulation and genome instability. An alternative scenario could be that piwi mutations directly affect genomic instability, and thus lead to increased transposon expression. We propose that the PIWI/piRNA pathway controls genome stability in several ways: suppression of transposons, direct regulation of chromatin architecture and regulation of genes that control important biological processes related to genome stability. The PIWI/piRNA pathway also regulates at least some, if not many, protein-coding genes, which further lends support to the idea that piwi genes may have broader functions beyond transposon repression. An intriguing possibility is that the PIWI/piRNA pathway is using transposon sequences to coordinate the expression of large groups of genes to regulate cellular function.

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Zili Inhibits Transforming Growth Factor-β Signaling by Interacting with Smad4

Cited by 32 publications

References 33 publications

Piwil2 Inhibits Keratin 8 Degradation through Promoting p38-Induced Phosphorylation To Resist Fas-Mediated Apoptosis

Piwil2 Inhibits Keratin 8 Degradation through Promoting p38-Induced Phosphorylation To Resist Fas-Mediated Apoptosis

Piwi-Like 2 Mediates Fibroblast Growth Factor Signaling during Gastrulation of Zebrafish Embryo

Untangling the web: The diverse functions of the PIWI/piRNA pathway

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