Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

Zhang, J; Zhu, Feng; X, Li; Z, Dong; Xu, Yiming; Peng, Cong; S, Li; Cho, Yong‐Yeon; Yao, Kangde; Ta, Zykova; Bode, AM

doi:10.1038/onc.2011.369

Cited by 25 publications

(22 citation statements)

References 36 publications

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“…This is in agreement with the fact that SE mainly localizes to nuclear D‐bodies (Fang and Spector, ), and that Arabidopsis RACK1 was present in the cytosol and nucleus in planta (Figure d). Some RACK1 targets have been reported to be stabilized or destabilized upon binding (Liu et al ., ; Zhang et al ., ), but we found that the amounts of SE remained unchanged in rack1 mutants (Figure e). These results suggest that RACK1 does not influence SE protein levels.…”

Section: Resultsmentioning

confidence: 61%

“…Mammalian RACK1 directly regulates transcription of the brain‐derived neurotrophic factor ( BDNF ) gene by physical association with a distinct promoter region and induction of acetylation of histone H4 (He et al ., ). RACK1 also indirectly influences transcription by interfering with the DNA binding capacity or reducing the stability of certain transcription factors (Okano et al ., ; Liu et al ., ; Zhang et al ., ). Whether Arabidopsis RACK1 directly associates with certain MIRNA genes or whether RACK1 regulates the activity of transcription factors that bind to the promoters of MIRNA genes is an interesting subject for future research.…”

Section: Discussionmentioning

confidence: 97%

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RACK1 scaffold proteins influence miRNA abundance in Arabidopsis

et al. 2013

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SUMMARYMicroRNAs (miRNAs) regulate plant development by post-transcriptional regulation of target genes. In Arabidopsis thaliana, DCL1 processes precursors (pri-miRNAs) to miRNA duplexes, which associate with AGO1. Additional proteins act in concert with DCL1 (e.g. HYL1 and SERRATE) or AGO1 to facilitate efficient and precise pri-miRNA processing and miRNA loading, respectively. In this study, we show that the accumulation of plant microRNAs depends on RECEPTOR FOR ACTIVATED C KINASE 1 (RACK1), a scaffold protein that is found in all higher eukaryotes. miRNA levels are reduced in rack1 mutants, and our data suggest that RACK1 affects the microRNA pathway via several distinct mechanisms involving direct interactions with known microRNA factors: RACK1 ensures the accumulation and processing of some pri-miRNAs, directly interacts with SERRATE and is part of an AGO1 complex. As a result, mutations in RACK1 lead to over-accumulation of miRNA target mRNAs, which are important for ABA responses and phyllotaxy, for example. In conclusion, our study identified complex functioning of RACK1 proteins in the Arabidopsis miRNA pathway; these proteins are important for miRNA production and therefore plant development.

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Section: Resultsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 97%

RACK1 scaffold proteins influence miRNA abundance in Arabidopsis

et al. 2013

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“…As an inhibitor of c‐Jun ubiquitination, it was surprising that PRR7 forms a high‐affinity complex with FBW7 and c‐Jun (Fig F). However, other inhibitors of FBW7 such as NEMO and Rack1 function in a similar way (Kim et al , ; Zhang et al , ). Rack1 blocks phospho‐c‐Jun ubiquitination by forming a high‐affinity ternary complex with FBW7 and non‐phosphorylated c‐Jun (Zhang et al , ), which allows transcriptionally active phospho‐c‐Jun to escape degradation.…”

Section: Discussionmentioning

confidence: 92%

Synaptonuclear messenger PRR 7 inhibits c‐Jun ubiquitination and regulates NMDA ‐mediated excitotoxicity

et al. 2016

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Elevated c-Jun levels result in apoptosis and are evident in neurodegenerative disorders such as Alzheimer's disease and dementia and after global cerebral insults including stroke and epilepsy. NMDA receptor (NMDAR) antagonists block c-Jun upregulation and prevent neuronal cell death following excitotoxic insults. However, the molecular mechanisms regulating c-Jun abundance in neurons are poorly understood. Here, we show that the synaptic component Proline rich 7 (PRR7) accumulates in the nucleus of hippocampal neurons following NMDAR activity. We find that PRR7 inhibits the ubiquitination of c-Jun by E3 ligase SCF FBW7 (FBW7), increases c-Jun-dependent transcriptional activity, and promotes neuronal death. Microarray assays show that PRR7 abundance is directly correlated with transcripts associated with cellular viability. Moreover, PRR7 knockdown attenuates NMDARmediated excitotoxicity in neuronal cultures in a c-Jun-dependent manner. Our results show that PRR7 links NMDAR activity to c-Jun function and provide new insights into the molecular processes that underlie NMDAR-dependent excitotoxicity.

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“…22,47,48 RACK1 can also promote this feed-forward signaling loop by inhibiting the proteasomal degradation of c-Jun. 49 The involvement of RACK1 in the initiation and progression of tumors and in their resistance to therapy has raised the possibility that it could be an appropriate target for the development of therapeutic drugs. However, optimism for this idea is tempered by the findings that RACK1 has several properties consistent with a tumor suppressor function.…”

Section: Monographsmentioning

confidence: 99%

RACK1 Function in Cell Motility and Protein Synthesis

et al. 2013

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The receptor for activated C kinase 1 (RACK1) serves as an adaptor for a number of proteins along the MAPK, protein kinase C, and Src signaling pathways. The abundance and near ubiquitous expression of RACK1 reflect its role in coordinating signaling molecules for many critical biological processes, from mRNA translation to cell motility to cell survival and death. Complete deficiency of Rack1 is embryonic lethal, but the recent development of genetic Rack1 hypomorphic mice has highlighted the central role that RACK1 plays in cell movement and protein synthesis. This review focuses on the importance of RACK1 in these processes and places the recent work in the larger context of understanding RACK1 function.

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Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

Cited by 25 publications

References 36 publications

RACK1 scaffold proteins influence miRNA abundance in Arabidopsis

RACK1 scaffold proteins influence miRNA abundance in Arabidopsis

Synaptonuclear messenger PRR 7 inhibits c‐Jun ubiquitination and regulates NMDA ‐mediated excitotoxicity

RACK1 Function in Cell Motility and Protein Synthesis

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