Systematic identification of regulatory proteins critical for T-cell activation

Chu, Peter C.; Pardo, Jorge; Zhao, Hang; Li, Connie C.; Pali, Erlina S.; Shen, Mary; Qu, Kun; Yu, Shichao; Huang, Betty; Yu, Peiwen; Masuda, Esteban; Molineaux, Susan M.; Frank, Konstantin; Aversa, Gregorio; Vries, Jan de; Payan, Donald G.; Liao, Xiang

doi:10.1186/1475-4924-2-21

Cited by 58 publications

(20 citation statements)

References 86 publications

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“…They introduced full-length cDNA clone resources (although they were not non-redundant in those days), in which each of the cDNAs was inserted downstream of the eukaryotic promoter, and identified 299 and 68 kinds of genes which induce the expression of the luciferase reporter genes driven by authentic NF-κB and MAPK target consensus sequences, respectively. Similar approaches have also been reported by other groups [37,38].…”

Section: Cell-based Assayssupporting

confidence: 88%

Transcriptome Analyses of Human Genes and Applications for Proteome Analyses

Suzuki¹,

Sugano²

2006

CPPS

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By utilizing recently developed full-length cDNA technologies, large-scale cDNA sequencing was carried out by several cDNA projects. Now full-length cDNA resources cover the major part of the protein-coding human genes. Comprehensive analyses of the collected full-length cDNA data revealed not only the complete sequences of thousands of novel gene transcripts but also novel alternatively spliced isoforms of hitherto identified genes. However, it was not as easy as expected to deduce their encoded amino acid sequences based solely on the full-length cDNA sequences. It was neither always the case that the longest open reading frame corresponded to the real protein coding region nor that the first ATG was the translation initiator codon. Also, proteome-wide mass-spectrometry analysis has shown that there is an unexpectedly large population of small proteins, encoded by so-called upstream open reading frames, within the cell. Since sound manual annotations by experts were still indispensable to address these problems, an international meeting to make transcriptome-wide functional annotations of cDNAs was held, namely the H-invitational. In this meeting, functional annotations were made both manually and computationally for most of the pre-existing full-length cDNAs collected from world-wide cDNA projects. The achieved integrated information for each of the cDNAs was published as a database. It was also shown that the full-length cDNA data were useful for identifying alternative splicing variants, exact transcriptional start sites of the mRNAs and the adjacent promoter regions. Rapidly accumulating genome data as well as versatile use of the transcriptome information will shortly lay a firm foundation for proteome-level understanding of human gene networks.

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Section: Cell-based Assayssupporting

confidence: 88%

Transcriptome Analyses of Human Genes and Applications for Proteome Analyses

Suzuki¹,

Sugano²

2006

CPPS

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“…NM_017831) and identified from a retroviral vector-based T cell surface activation marker screen [17]. It associates with membranes and is excluded from the nucleus through myristoylation.…”

Section: Discussionmentioning

confidence: 99%

RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation

Yang

Zhou

et al. 2015

Cell Physiol Biochem

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Background/Aims: Although early studies show that Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein ligase, in the regulation of p53. Methods and Results: RNF125 physically interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST-pull down assay, and a C72/75A mutation of RNF125 did not interfere with this interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent manner, whereas knockdown of RNF125 by RNA interference increased the level of p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53 and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53 functions including p53-dependent transactivation and growth inhibition. Conclusion: Our data suggest that RNF125 negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation.

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“…T cell responses to S1P 1 are impaired in HIV-1 infected individuals, perhaps contributing to lymphadenopathy [110] . S1P 1 and CD69 are mutual antagonists [110] , [111] and CD69 expression inhibits S1P 1 -dependent egress from lymphoid organs until later in the activation cascade, when CD69 levels decline [112] . CD69 also regulates chemokine expression and T cell accumulation in the intestine [113] .…”

Section: Discussionmentioning

confidence: 99%

Suppression of Foxo1 Activity and Down-Modulation of CD62L (L-Selectin) in HIV-1 Infected Resting CD4 T Cells

et al. 2014

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HIV-1 hijacks and disrupts many processes in the cells it infects in order to suppress antiviral immunity and to facilitate its replication. Resting CD4 T cells are important early targets of HIV-1 infection in which HIV-1 must overcome intrinsic barriers to viral replication. Although resting CD4 T cells are refractory to infection in vitro, local environmental factors within lymphoid and mucosal tissues such as cytokines facilitate viral replication while maintaining the resting state. These factors can be utilized in vitro to study HIV-1 replication in resting CD4 T cells. In vivo, the migration of resting naïve and central memory T cells into lymphoid tissues is dependent upon expression of CD62L (L-selectin), a receptor that is subsequently down-modulated following T cell activation. CD62L gene transcription is maintained in resting T cells by Foxo1 and KLF2, transcription factors that maintain T cell quiescence and which regulate additional cellular processes including survival, migration, and differentiation. Here we report that HIV-1 down-modulates CD62L in productively infected naïve and memory resting CD4 T cells while suppressing Foxo1 activity and the expression of KLF2 mRNA. Partial T cell activation was further evident as an increase in CD69 expression. Several other Foxo1- and KLF2-regulated mRNA were increased or decreased in productively infected CD4 T cells, including IL-7rα, Myc, CCR5, Fam65b, S1P1 (EDG1), CD52, Cyclin D2 and p21CIP1, indicating a profound reprogramming of these cells. The Foxo1 inhibitor AS1842856 accelerated de novo viral gene expression and the sequella of infection, supporting the notion that HIV-1 suppression of Foxo1 activity may be a strategy to promote replication in resting CD4 T cells. As Foxo1 is an investigative cancer therapy target, the development of Foxo1 interventions may assist the quest to specifically suppress or activate HIV-1 replication in vivo.

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Systematic identification of regulatory proteins critical for T-cell activation

Cited by 58 publications

References 86 publications

Transcriptome Analyses of Human Genes and Applications for Proteome Analyses

Transcriptome Analyses of Human Genes and Applications for Proteome Analyses

RNF125 is a Ubiquitin-Protein Ligase that Promotes p53 Degradation

Suppression of Foxo1 Activity and Down-Modulation of CD62L (L-Selectin) in HIV-1 Infected Resting CD4 T Cells

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