Structure of the SCAN Domain of Human Paternally Expressed Gene 3 Protein

Rimsa, V.; Eadsforth, T.C.; Hunter, William N.

doi:10.1371/journal.pone.0069538

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…Moreover, we used the interaction partners, from I2D , for which at least one experimental structure was available in the PDB . We also included two additional SCAN domain proteins, the Zfp206 and Peg3 [PDB entries 4E6S (Liang et al, 2012) chain A and 4BHX (Rimsa et al, 2013) chain A, respectively] to further investigate the role of SCAN-mediated hetero-dimerization. For analyses, we retained only those complexes with a predicted docking energy lower than −2.39 kcal/mol (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

Nygaard

Terkelsen

Olsen

et al. 2016

Front. Mol. Biosci.

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SCAN domains in zinc-finger transcription factors are crucial mediators of protein-protein interactions. Up to 240 SCAN-domain encoding genes have been identified throughout the human genome. These include cancer-related genes, such as the myeloid zinc finger 1 (MZF1), an oncogenic transcription factor involved in the progression of many solid cancers. The mechanisms by which SCAN homo- and heterodimers assemble and how they alter the transcriptional activity of zinc-finger transcription factors in cancer and other diseases remain to be investigated. Here, we provide the first description of the conformational ensemble of the MZF1 SCAN domain cross-validated against NMR experimental data, which are probes of structure and dynamics on different timescales. We investigated the protein-protein interaction network of MZF1 and how it is perturbed in different cancer types by the analyses of high-throughput proteomics and RNASeq data. Collectively, we integrated many computational approaches, ranging from simple empirical energy functions to all-atom microsecond molecular dynamics simulations and network analyses to unravel the effects of cancer-related substitutions in relation to MZF1 structure and interactions.

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Section: Resultsmentioning

confidence: 99%

The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

Nygaard

Terkelsen

Olsen

et al. 2016

Front. Mol. Biosci.

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“…To date, the spatial structures of the SCAN domains of the proteins Zfp206 [ 107 ], PEG3 [ 108 ], ZNF24, ZNF174 [ 105 ], and MZF-1 [ 109 ], which have a high degree of homology, have been resolved ( Fig. 5B ).…”

Section: Transcription Factors With a Cluster Of C2h2 Domains And An mentioning

confidence: 99%

C2H2 Zinc Finger Proteins: The Largest but Poorly Explored Family of Higher Eukaryotic Transcription Factors

et al. 2017

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The emergence of whole-genome assays has initiated numerous genome-wide studies of transcription factor localizations at genomic regulatory elements (enhancers, promoters, silencers, and insulators), as well as facilitated the uncovering of some of the key principles of chromosomal organization. However, the proteins involved in the formation and maintenance of the chromosomal architecture and the organization of regulatory domains remain insufficiently studied. This review attempts to collate the available data on the abundant but still poorly understood family of proteins with clusters of the C2H2 zinc finger domains. One of the best known proteins of this family is a well conserved protein known as CTCF, which plays a key role in the establishment of the chromosomal architecture in vertebrates. The distinctive features of C2H2 zinc finger proteins include strong and specific binding to a long and unique DNA recognition target sequence and rapid expansion within various animal taxa during evolution. The reviewed data support a proposed model according to which many of the C2H2 proteins have functions that are similar to those of the CTCF in the organization of the chromatin architecture.

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“…Structurally, PEG3 is composed of an N-terminal SCAN domain required for protein–protein interactions and an extended C terminus of 12 C 2 H 2 Krüppel-like zinc fingers (interspersed with proline-rich regions) for DNA binding and transcriptional regulation ( Fig. 2 G ) ( 23 , 58 , 59 ). Generating HA-tagged truncation fragments ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy

Neill

Sharpe

Owens³

et al. 2017

Journal of Biological Chemistry

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Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires paternally expressed gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of transcription factor EB (TFEB), a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in human umbilical vein endothelial and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMP-activated protein kinase (AMPK), a major decorin-activated energy sensor kinase, prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient- and energy-independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB.

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Structure of the SCAN Domain of Human Paternally Expressed Gene 3 Protein

Cited by 9 publications

References 47 publications

The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

C2H2 Zinc Finger Proteins: The Largest but Poorly Explored Family of Higher Eukaryotic Transcription Factors

Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy

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