A human MAP kinase interactome

Bandyopadhyay, Sourav; Chiang, Chih-Yuan; Srivastava, Jyoti; Gersten, Merril; White, Suhaila; Bell, Russell; Kurschner, Cornelia; Martin, Christopher; Smoot, Mike; Sahasrabudhe, Sudhir; Barber, Diane L.; Chanda, Sumit K.; Ideker, Trey

doi:10.1038/nmeth.1506

Cited by 189 publications

(154 citation statements)

References 44 publications

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“…12 In addition, this study found that MBD5 and RAI1, along with FMR1, are involved in circadian and mTOR signaling pathways, both associated with sleep disturbance. 12 MBD5 appears to share molecular relationships with ASD-associated genes, including protein-binding relationships with FMR1, 31 APC, 32 and MEF2C 32 ( Figure 5). Further, based on our co-expression studies, haploinsufficiency of MBD5 results in dysregulation of other ASD-associated genes, including UBE3A (AS), RAI1 (SMS), TCF4 (PTHS), MEF2C (OMIM#613443), and FMR1 (FXS) ( Figure 5).…”

Section: Mbd5 Functions In Transcriptional Regulationmentioning

confidence: 99%

Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Mullegama

Elsea

2016

Eur J Hum Genet

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Section: Mbd5 Functions In Transcriptional Regulationmentioning

confidence: 99%

Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Mullegama

Elsea

2016

Eur J Hum Genet

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“…These included 496 positive and 434 negative correlations between nuclear and mtDNA gene expression in CEU, plus 203 positive and 184 negative correlations in YRI. A total of 63 of these genes (29 positive and 34 negative) were found in common between CEU and YRI (Figure 2), including 15 ribosomal protein genes, ACIN1 (apoptotic chromatin condensation inducer protein activated by caspase-3, Figure 3a), and ZSWIM1 (zinc-finger SWIM domain-containing protein indirectly interacting with MT-ND2 through MAPK14, 35 Figure 3b). GO analyses indicated that positively-correlated nuclear genes were often involved in the regulation of transcription; those negatively-correlated were more likely to be involved in translation (for details, see Supplementary Table 2).…”

Section: Coordinated Expression Of Mtdna Genesmentioning

confidence: 99%

Population-level expression variability of mitochondrial DNA-encoded genes in humans

et al. 2014

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Human mitochondria contain multiple copies of a circular genome made up of double-stranded DNA (mtDNA) that encodes proteins involved in cellular respiration. Transcript abundance of mtDNA-encoded genes varies between human individuals, yet the level of variation in the general population has not been systematically assessed. In the present study, we revisited large-scale RNA sequencing data generated from lymphoblastoid cell lines of HapMap samples of European and African ancestry to estimate transcript abundance and quantify expression variation for mtDNA-encoded genes. In both populations, we detected up to over 100-fold difference in mtDNA gene expression between individuals. The marked variation was not due to differences in mtDNA copy number between individuals, but was shaped by the transcription of hundreds of nuclear genes. Many of these nuclear genes were co-expressed with one another, resulting in a module-enriched co-expression network. Significant correlations in expression between genes of the mtDNA and nuclear genomes were used to identify factors involved with the regulation of mitochondrial functions. In conclusion, we determined the baseline amount of variability in mtDNA gene expression in general human populations and cataloged a complete set of nuclear genes whose expression levels are correlated with those of mtDNA-encoded genes. Our findings will enable the integration of information from both mtDNA and nuclear genetic systems, and facilitate the discovery of novel regulatory pathways involving mitochondrial functions.

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“…Previous studies support the utility of analyzing network interactions in receptorspecific pathways, to generate insights into signaling mechanisms. Furthermore, they also emphasized the potential of this approach for identifying new drug targets (Tu et al 2009;Astsaturov et al 2010;Bandyopadhyay et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Delineation of key regulatory elements identifies points of vulnerability in the mitogen-activated signaling network

Jailkhani

Ravichandran²,

Hegde³

et al. 2011

Genome Res.

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Drug development efforts against cancer are often hampered by the complex properties of signaling networks. Here we combined the results of an RNAi screen targeting the cellular signaling machinery, with graph theoretical analysis to extract the core modules that process both mitogenic and oncogenic signals to drive cell cycle progression. These modules encapsulated mechanisms for coordinating seamless transition of cells through the individual cell cycle stages and, importantly, were functionally conserved across different cancer cell types. Further analysis also enabled extraction of the core signaling axes that progressively guide commitment of cells to the division cycle. Importantly, pharmacological targeting of the least redundant nodes in these axes yielded a synergistic disruption of the cell cycle in a tissue-type-independent manner. Thus, the core elements that regulate temporally distinct stages of the cell cycle provide attractive targets for the development of multi-module-based chemotherapeutic strategies.

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A human MAP kinase interactome

Cited by 189 publications

References 44 publications

Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Population-level expression variability of mitochondrial DNA-encoded genes in humans

Delineation of key regulatory elements identifies points of vulnerability in the mitogen-activated signaling network

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