Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Lv, Yanrong; Zhang, Kai; Gao, Haidong

doi:10.1128/mcb.00524-14

Cited by 18 publications

(9 citation statements)

References 36 publications

(42 reference statements)

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“…Although Parafibromin lacks the canonical PPxY motif, it possesses a PPxY-related PxxY (PAAY) sequence that contains Tyr290, one of three tyrosine phosphorylation sites, which plays the most important role in the Parafibromin/β-catenin interaction ( Takahashi et al., 2011 ). It has been reported that the PxxY sequence can also interact with the WW domain ( Lv et al., 2014 ), and indeed we found that stable binding with TAZ requires dephosphorylated PAAY in addition to the β-catenin-binding region of Parafibromin. Through the interaction, dephosphorylated Parafibromin stimulates the co-activator function of TAZ.…”

Section: Discussionsupporting

confidence: 76%

Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by Tyrosine Phosphorylation Status of Parafibromin

et al. 2018

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SummaryYAP and TAZ, the Hippo signal-regulated transcriptional co-activators, play crucial roles in morphogenesis and organogenesis. Here we report that the YAP/TAZ activities are stimulated upon complex formation with Parafibromin, which undergoes tyrosine phosphorylation and dephosphorylation by kinases such as PTK6 and phosphatases such as SHP2, respectively. Furthermore, TAZ and the Wnt effector β-catenin interact cooperatively with tyrosine-dephosphorylated Parafibromin, which synergistically stimulates the co-activator functions of TAZ and β-catenin. On the other hand, YAP is selectively activated through binding with tyrosine-phosphorylated Parafibromin, which does not interact with β-catenin and thus cannot co-activate YAP and β-catenin. These findings indicate that Parafibromin inversely regulates the activities of YAP and TAZ depending on its tyrosine phosphorylation status. They also suggest that YAP and TAZ exert their redundant and non-redundant biological actions through mutually exclusive interaction with Parafibromin, which is regulated by a balance of kinase and phosphatase activities toward Parafibromin.

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Section: Discussionsupporting

confidence: 76%

Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by Tyrosine Phosphorylation Status of Parafibromin

et al. 2018

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“…Ubiquitination is a reversible process, and deubiquitinating enzymes (DUBs) cleave ubiquitin moieties from their substrates, to tightly control ubiquitination levels ( 21 ). It has been revealed that many ribosomal proteins, among both the small and large subunits ( 22 , 23 ), as well as several eIFs, including eIF5A ( 24 ), Paip1 ( 25 ), Paip2 ( 26 ), 4E-BP1 ( 27 ) and eIF2B epsilon ( 28 ) are ubiquitinated. Moreover, the cap-binding protein eIF4E is reported to be primarily ubiquitinated at Lys-159 and ubiquitination of eIF4E reduces its ability to bind eIF4G ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1

Cheng

Chaerkady

et al. 2017

Nucleic Acids Research

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Controlling translation initiation is an efficient way to regulate gene expression at the post-transcriptional level. However, current knowledge regarding regulatory proteins and their modes of controlling translation initiation is still limited. In this study, we employed tandem affinity purification and mass spectrometry to screen for unknown proteins associated with the translation initiation machinery. Ubiquitin specific peptidase 9, X-linked (USP9X), was identified as a novel binding partner, that interacts with the eukaryotic translation initiation factor 4B (eIF4B) in a mRNA-independent manner. USP9X-deficient cells presented significantly impaired nascent protein synthesis, cap-dependent translation initiation and cellular proliferation. USP9X can selectively alter the translation of pro-oncogenic mRNAs, such as c-Myc and XIAP. Moreover, we found that eIF4A1, which is primarily ubiquitinated at Lys-369, is the substrate of USP9X. USP9X dysfunction increases the ubiquitination of eIF4A1 and enhances its degradation. Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deubiquitination of eIF4A1, which offers new insight in understanding the pivotal role of USP9X in human malignancies and neurodevelopmental disorders.

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“…Among the most significantly differentially-connected genes confirmed in all three studies, we found poly(A)-binding protein-interacting protein 1 ( PAIP1 ) that stimulates translational initiation by inducing the circularization of mRNA [ 42 ]. Deregulation at this step of the translation process leads to altered gene expression, which in turn modifies cell growth.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Differential Connectivity in Gene Co-Expression Networks in Multiple Sclerosis

Creanza

Liguori

Liuni

et al. 2016

IJMS

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Differential gene expression analyses to investigate multiple sclerosis (MS) molecular pathogenesis cannot detect genes harboring genetic and/or epigenetic modifications that change the gene functions without affecting their expression. Differential co-expression network approaches may capture changes in functional interactions resulting from these alterations. We re-analyzed 595 mRNA arrays from publicly available datasets by studying changes in gene co-expression networks in MS and in response to interferon (IFN)-β treatment. Interestingly, MS networks show a reduced connectivity relative to the healthy condition, and the treatment activates the transcription of genes and increases their connectivity in MS patients. Importantly, the analysis of changes in gene connectivity in MS patients provides new evidence of association for genes already implicated in MS by single-nucleotide polymorphism studies and that do not show differential expression. This is the case of amiloride-sensitive cation channel 1 neuronal (ACCN1) that shows a reduced number of interacting partners in MS networks, and it is known for its role in synaptic transmission and central nervous system (CNS) development. Furthermore, our study confirms a deregulation of the vitamin D system: among the transcription factors that potentially regulate the deregulated genes, we find TCF3 and SP1 that are both involved in vitamin D3-induced p27Kip1 expression. Unveiling differential network properties allows us to gain systems-level insights into disease mechanisms and may suggest putative targets for the treatment.

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Paip1, an Effective Stimulator of Translation Initiation, Is Targeted by WWP2 for Ubiquitination and Degradation

Cited by 18 publications

References 36 publications

Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by Tyrosine Phosphorylation Status of Parafibromin

Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by Tyrosine Phosphorylation Status of Parafibromin

USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1

Meta-Analysis of Differential Connectivity in Gene Co-Expression Networks in Multiple Sclerosis

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