PJA1, Encoding a RING-H2 Finger Ubiquitin Ligase, Is a Novel Human X Chromosome Gene Abundantly Expressed in Brain

Yü, Ping; Chen, Yiwang; Tagle, Danilo A.; Cai, Tao

doi:10.1006/geno.2002.6770

Cited by 52 publications

(49 citation statements)

References 40 publications

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“…Transcript has been localized in brain, liver, kidney, and embryo [22]; expression has been seen in wound healing [23], brain [24], and in liver cells [22]. Although MageD1 was initially implicated as a substrate of Praja1 [25], this data were consistent with later studies showing that the MAGE family of proteins are binding partners and positive cofactors of RING finger ligases [26].…”

Section: Introductionsupporting

confidence: 64%

“…Praja1 is an E3 ubiquitin ligase implicated in bone and liver development as well as memory formation and X-linked mental retardation [21][22][23][24]. Transcript has been localized in brain, liver, kidney, and embryo [22]; expression has been seen in wound healing [23], brain [24], and in liver cells [22].…”

Section: Introductionmentioning

confidence: 98%

“…Nevertheless, the interactions between the MAGE family proteins and RING finger ligases do not formally exclude the possibility that RING finger ligases ubiquitylate particular MAGE proteins, either for proteasomal destruction or non-degradative functions. Another cofactor of Praja1, UBE2D2, has been shown to interact in vitro and in vivo [24], making this a strong candidate for the functional E2 for Praja1. Proteomic study of the interaction network and substrates of Praja1 would provide better insight into this intriguing E3, and provide the basis for further experimentation.…”

Section: Introductionmentioning

confidence: 99%

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Protein Microarrays for the Identification of Praja1 E3 Ubiquitin Ligase Substrates

Loc’h

Eddins

Strickler

2011

Cell Biochem Biophys

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Although they are the primary determinants of substrate specificity, few E3-substrate pairs have been positively identified, and few E3's profiled in a proteomic fashion. Praja1 is an E3 implicated in bone development and highly expressed in brain. Although it has been well studied relative to the majority of E3's, little is known concerning the repertoire of proteins it ubiquitylates. We sought to identify high confidence substrates for Praja1 from an unbiased proteomic profile of thousands of human proteins using protein microarrays. We first profiled Praja1 activity against a panel of E2's to identify its optimal partner in vitro. We then ubiquitylated multiple, identical protein arrays and detected putative substrates with reagents that vary in ubiquitin recognition according to the extent of chain formation. Gene ontology clustering identified putative substrates consistent with information previously known about Praja1 function, and provides clues into novel aspects of this enzyme's function.

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Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protein Microarrays for the Identification of Praja1 E3 Ubiquitin Ligase Substrates

Loc’h

Eddins

Strickler

2011

Cell Biochem Biophys

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“…On the contrary, glial cell-associated genes, such as Mbp, Plp, and S100b, and neuron-associated genes, such as Apoe, Pja2, Syn2, Syp, Synpr, and Nfl are downregulated in the embryonic stage [36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 95%

Gene Expression Profiling of Rat Cerebral Cortex Development Using cDNA Microarrays

Lee

2008

Neurochem Res

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A large amount of genetic information is devoted to brain development. In this study, the cortical development in rats at eight developmental time points (four embryonic [E15, E16, E18, E20] and four postnatal [P0, P7, P14, P21]) was studied using a rat brain 10K cDNA microarray. Significant differential expression was observed in 467 of the 9,805 genes represented on the microarray. Two major Gene Ontology classes-cell differentiation and cell-cell signaling-were found to be important for cortical development. Genes for ribosomal proteins, heterogeneous nuclear ribonucleoproteins, and tubulin proteins were up-regulated in the embryonic stage, coincidently with extensive proliferation of neural precursor cells as the major component of the cerebral cortex. Genes related to neurogenesis, including neurite regeneration, neuron development, and synaptic transmission, were more active in adulthood, when the cerebral cortex reached maturity. The many developmentally modulated genes identified by this approach will facilitate further studies of cortical functions.

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“…To date very little is known about the role of these proteins in the central nervous system. PRAJA-1 is a E2-dependent E3 ubiquitin ligase that is abundantly expressed in the brain (46), and has as its putative substrates the postsynaptic proteins Homer2, CAMK1G, EPHB3 and SEPT1 (47). PRAJA-1 has been implicated in learning and memory associated with fear conditioning (48).…”

Section: Discussionmentioning

confidence: 99%

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis

Stockton¹,

Gomes²,

Liu³

et al. 2015

Molecular & Cellular Proteomics

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Despite its efficacy, the use of morphine for the treatment of chronic pain remains limited because of the rapid development of tolerance, dependence and ultimately addiction. These undesired effects are thought to be because of alterations in synaptic transmission and neuroplasticity within the reward circuitry including the striatum. In this study we used subcellular fractionation and quantitative proteomics combined with computational approaches to investigate the morphine-induced protein profile changes at the striatal postsynaptic density. Over 2,600 proteins were identified by mass spectrometry analysis of subcellular fractions enriched in postsynaptic density associated proteins from saline or morphine-treated striata. Among these, the levels of 34 proteins were differentially altered in response to morphine. These include proteins involved in G-protein coupled receptor signaling, regulation of transcription and translation, chaperones, and protein degradation pathways. The altered expression levels of several of these proteins was validated by Western blotting analysis. Using Genes2Fans software suite we connected the differentially expressed proteins with proteins identified within the known background protein-protein interaction network. This led to the generation of a network consisting of 116 proteins with 40 significant intermediates. To validate this, we confirmed the presence of three proteins predicted to be significant intermediates: caspase-3, receptor-interacting serine/threonine protein kinase 3 and NEDD4 (an E3-ubiquitin ligase identified as a neural precursor cell expressed developmentally down-regulated protein 4). Because this morphine-regulated network predicted alterations in proteasomal degradation, we examined the global ubiquitination state of postsynaptic density proteins and found it to be substantially altered. Together, these findings suggest a role for protein degradation and for the ubiquitin/proteasomal system in the etiology of opiate dependence and addiction. Morphine and other opiates are the drugs of choice for the treatment of both severe and chronic pain. However, the utility of these compounds in the clinical setting is limited because of the rapid development of tolerance, physical dependence and addiction. The underlying cellular and molecular alterations through which chronic opiate exposure results in the persistent behavioral phenomenon of addiction remain poorly understood. However, there is evidence suggesting that the molecular composition of synapses within the reward circuitry of the central nervous system, particularly in the striatum, may be significantly altered (1). Moreover, given the critical involvement of the striatum in translating emotional or rewarding stimuli into motivated behaviors, alterations in this region induced by morphine and other abused drugs could contribute significantly to the pathophysiological responses at the heart of addiction (2). Although the debate surrounding the molecular and cellular mechanisms by which repeated drug adminis...

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PJA1, Encoding a RING-H2 Finger Ubiquitin Ligase, Is a Novel Human X Chromosome Gene Abundantly Expressed in Brain

Cited by 52 publications

References 40 publications

Protein Microarrays for the Identification of Praja1 E3 Ubiquitin Ligase Substrates

Protein Microarrays for the Identification of Praja1 E3 Ubiquitin Ligase Substrates

Gene Expression Profiling of Rat Cerebral Cortex Development Using cDNA Microarrays

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis

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