Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Cho, Hee Jun; Park, Sun Mi; Hwang, Eun Mi; Baek, Kyoung Eun; Kim, In Kyu; Nam, In Koo; Im, Min Ju; Park, Seung Ho; Bae, Seran; Park, Jae Yong; Yoo, Ji Myong

doi:10.1074/jbc.m109.091413

Cited by 50 publications

(43 citation statements)

References 29 publications

(27 reference statements)

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“…specific (Salvador et al 2013). It has been suggested that GADD45B may enhance or mitigate FAS-mediated apoptosis, depending on the cell type (Zazzeroni et al 2003, Cho et al 2010, thus the increase in GADD45B mRNA levels occurring with increased FASLG mRNA abundance may be part of either the apoptotic mechanism or a DNA repair mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

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Mycotoxins can reduce fertility and development in livestock, notably in pigs and poultry, although the effect of most mycotoxins on reproductive function in cattle has not been established. One major mycotoxin, deoxynivalenol (DON), not only targets immune cells and activates the ribotoxic stress response (RSR) involving MAPK activation, but also inhibits oocyte maturation in pigs. In this study, we determined the effect of DON on bovine granulosa cell function using a serum-free culture system. Addition of DON inhibited estradiol and progesterone secretion, and reduced levels of mRNA encoding estrogenic (CYP19A1) but not progestogenic (CYP11A1 and STAR) proteins. Cell apoptosis was increased by DON, which also increased FASLG mRNA levels. The mechanism of action of DON was assessed by western blotting and PCR experiments. Addition of DON rapidly and transiently increased phosphorylation of MAPK3/1, and resulted in a more prolonged phosphorylation of MAPK14 (p38) and MAPK8 (JNK). Activation of these pathways by DON resulted in time-and dose-dependent increases in abundance of mRNA encoding the transcription factors FOS, FOSL1, EGR1, and EGR3. We conclude that DON is deleterious to granulosa cell function and acts through a RSR pathway.

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Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

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“…However, GADD45B has a number of additional activities that could be necessary for the viral lytic cycle. These include promoting DNA demethylation and Retinoblastoma (Rb) inactivation, processes that are important for a number of DNA viruses, including KSHV [74][75][76][77][78][79]. If our hypothesis that there are numerous SREs throughout the transcriptome is correct, it is likely that individual viruses require only a subset of these host genes for replication.…”

Section: Discussionmentioning

confidence: 99%

Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

Muller

Glaunsinger

2017

Preprint

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During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3' UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.

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“…Both Gadd45b and Gadd45g interact with p21, and Gadd45b positively regulates its expression in senescing chondrocytes (Ijiri et al 2005 ), although the result of this interaction is unclear in other tissues and contexts (Gao et al 2009 ). Gadd45b facilitates p38-mediated activation of retinoblastoma tumor suppressor protein (Rb) by enhancing their interaction after Fas stimulation in murine hepatocytes (Cho et al 2010 ). It also mediates TGF-induced apoptosis in murine hepatic cells in a p38-and Smad-dependent manner and both Gadd45b and Gadd45g overexpression-induced apoptosis in HeLa cells.…”

Section: Roles For Gadd45b and Gadd45gmentioning

confidence: 98%

Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis

Salvador

Brown-Clay

Fornace

2013

Advances in Experimental Medicine and Biology

297

250

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The first identified Gadd45 gene, Gadd45a, encodes a ubiquitously expressed protein that is often induced by DNA damage and other stress signals associated with growth arrest and apoptosis. This protein and the other two members of this small gene family, Gadd45b and Gadd45g, have been implicated in a variety of the responses to cell injury including cell cycle checkpoints, apoptosis, and DNA repair. In vivo, many of the prominent roles for the Gadd45 proteins are associated with signaling mediated by p38 mitogen-activated protein kinases (MAPK). Gadd45 proteins can contribute to p38 activation either by activation of upstream kinase(s) or by direct interaction. In vivo, there are important tissue and cell-type-specific differences in the roles for Gadd45 in MAPK signaling. In addition to being p53-regulated, Gadd45a has been found to contribute to p53 activation via p38. Like other stress and signaling proteins, Gadd45 proteins show complex regulation and numerous effectors.

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Gadd45b Mediates Fas-induced Apoptosis by Enhancing the Interaction between p38 and Retinoblastoma Tumor Suppressor

Cited by 50 publications

References 29 publications

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis

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