Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability

Ye, Buqing; Dai, Zhendong; Liu, Benyu; Wang, Rui; Li, Chong; Huang, Guanling; Wang, Shuo; Xia, Pengyan; Yang, Xuan; Kuwahara, K.; Sakaguchi, Nobuo; Fan, Zusen

doi:10.1002/stem.1580

Cited by 18 publications

(20 citation statements)

References 37 publications

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“…These results indicate that EID1 is degraded by the proteasome following ubiquitination by SCF FBXO21 . MDM2, rather than Cullin-RING ubiquitin ligase, is the ubiquitin ligase for EID1 (26,27). However, siRNA-mediated knockdown of MDM2 or RB1 did not stabilize EID1 protein in 293T cells (Fig.…”

Section: Identification Of Substrates For Uncharacterized Ubiquitin Lmentioning

confidence: 91%

A comprehensive method for detecting ubiquitinated substrates using TR-TUBE

Yoshida¹,

Saeki²,

Murakami³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

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The identification of substrates for ubiquitin ligases has remained challenging, because most substrates are either immediately degraded by the proteasome or processed by deubiquitinating enzymes (DUBs) to remove polyubiquitin. Although a methodology that enables detection of ubiquitinated proteins using ubiquitin Lys-e-Gly-Gly (diGly) remnant antibodies and MS has been developed, it is still insufficient for identification and characterization of the ubiquitin-modified proteome in cells overexpressing a particular ubiquitin ligase. Here, we show that exogenously expressed trypsin-resistant tandem ubiquitin-binding entity(ies) (TR-TUBE) protect polyubiquitin chains on substrates from DUBs and circumvent proteasome-mediated degradation in cells. TR-TUBE effectively associated with substrates ubiquitinated by an exogenously overexpressed ubiquitin ligase, allowing detection of the specific activity of the ubiquitin ligase and isolation of its substrates. Although the diGly antibody enabled effective identification of ubiquitinated proteins in cells, overexpression of an ubiquitin ligase and treatment with a proteasome inhibitor did not increase the level of diGly peptides specific for the ligase relative to the background level of diGly peptides, probably due to deubiquitination. By contrast, in TR-TUBE-expressing cells, the level of substrate-derived diGly peptides produced by the overexpressed ubiquitin ligase was significantly elevated. We developed a method for identifying the substrates of specific ubiquitin ligases using two enrichment strategies, TR-TUBE and diGly remnant antibodies, coupled with MS. Using this method, we identified target substrates of FBXO21, an uncharacterized F-box protein.ubiquitin-binding protein | ubiquitin ligase | ubiquitination

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Section: Identification Of Substrates For Uncharacterized Ubiquitin Lmentioning

confidence: 91%

A comprehensive method for detecting ubiquitinated substrates using TR-TUBE

Yoshida¹,

Saeki²,

Murakami³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

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“…DNase I sensibility assay. Cell nuclei were isolated and lysed for DNase I digestion as described (53). After digestion for 5 minutes at 37°C, total DNA was extracted and quantitative RT-PCR was performed with the indicated promoter-specific primers.…”

Section: Methodsmentioning

confidence: 99%

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

Zhu¹,

Wang²,

He³

et al. 2015

Journal of Clinical Investigation

Self Cite

137

124

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“…It has been proposed that EID1 needs to be degraded to stimulate differentiation, and that inhibition of p300 HAT activity, in particular, is mechanistically important. EID1 has also 8 been shown to interact with a pluripotency factor Pcid2, and thus affect the ability of stem cells to self-renew (69). It is possible that, in cancers originating in stem cells, the levels of EID1 may be important in maintaining tumour initiating cells.…”

Section: Sustaining Proliferation By Blocking Differentiationmentioning

confidence: 99%

F-box protein interactions with the hallmark pathways in cancer

Randle

Laman

2016

Seminars in Cancer Biology

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F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention.

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Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability

Cited by 18 publications

References 37 publications

A comprehensive method for detecting ubiquitinated substrates using TR-TUBE

A comprehensive method for detecting ubiquitinated substrates using TR-TUBE

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

F-box protein interactions with the hallmark pathways in cancer

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