The multifunctional human p100 protein 'hooks' methylated ligands

Shaw, Neil; Zhao, Min; Cheng, Chu Yong; Xu, Hao; Saarikettu, Juha; Li, Yang; Da, Yurong; Yao, Zhi; Silvennoinen, Olli; Yang, Jie; Liu, Zhijie; Wang, Bi-Cheng; Rao, Zihe

doi:10.1038/nsmb1269

Cited by 74 publications

(88 citation statements)

References 37 publications

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“…SND1 is generally regarded as a nuclear and/or cytoplasmic protein and in line with a number of reports, [26,45,46] we observed only extranuclear expression in b-cells. The defined architecture of SND1 provides distinct binding sites and functions [47]. Whereas the C-terminal Tudor domain flanked by SN regions is involved in regulation of splicing [48], the N-terminal tandem repeats of SN-like domains are required to complex co-activators and transcription factors [42,49], to capture and cleave RNA substrates [50], to link Ago2 within the RISC complex [51] and, as shown here, to bind directly the C 2 B domain of syt11.…”

Section: Discussionmentioning

confidence: 99%

Synaptotagmin 11 interacts with components of the RNA‐induced silencing complex RISC in clonal pancreatic β‐cells

et al. 2014

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a b s t r a c tSynaptotagmins are two C 2 domain-containing transmembrane proteins. The function of calciumsensitive members in the regulation of post-Golgi traffic has been well established whereas little is known about the calcium-insensitive isoforms constituting half of the protein family. Novel binding partners of synaptotagmin 11 were identified in b-cells. A number of them had been assigned previously to ER/Golgi derived-vesicles or linked to RNA synthesis, translation and processing. Whereas the C2A domain interacted with the Q-SNARE Vti1a, the C2B domain of syt11 interacted with the SND1, Ago2 and FMRP, components of the RNA-induced silencing complex (RISC). Binding to SND was direct via its N-terminal tandem repeats. Our data indicate that syt11 may provide a link between gene regulation by microRNAs and membrane traffic. Structured summary of protein interactions:Syt11C2A physically interacts with Vti1a by pull down (View interaction) Syt11C2B physically interacts with SND1, PDIA6, Vti1b, Vti1a, Ago2 and FMRP by pull down (View interaction) syt11C2B binds to SND1 by filter binding (View interaction) Syt11C2B physically interacts with EIF3A, PDIA6, NPM1, EIF3B, NCL, RS3, RS3A, CBR1, ANP32B, LOC683961, SET, SND1, TBB2C, RS10 and RS18 by pull down (View interaction) SND1 physically interacts with Ago2 by anti bait coip (View interaction)

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Section: Discussionmentioning

confidence: 99%

Synaptotagmin 11 interacts with components of the RNA‐induced silencing complex RISC in clonal pancreatic β‐cells

et al. 2014

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“…In contrast, several studies have also described SND1 as a mediator of multiple posttranscriptional processes via interactions with RNA and RNAassociated proteins. SND1 has been shown to associate with the U5 small nuclear ribonucleoprotein component of the spliceosome (39) and enhance spliceosome assembly and activity (26). A different approach identified SND1 as a component of the RNA-induced silencing complex and further determined SND1 to harbor broad scale (RNA and DNA) nuclease activity (25).…”

Section: Discussionmentioning

confidence: 99%

“…The SN domains are suggested to have nuclease activity (38), whereas the Tudor-SN domain is suggested to bind methylated protein substrates (39). To test whether MTDH could interact with the SN domains, Tudor-SN domain, or both, two HA-tagged SND1 deletion mutant constructs were created, one containing the four SN repeat domains and the other containing the Tudor-SN domain.…”

Section: Identification Of Snd1 As An Mtdh-interacting Protein-tomentioning

confidence: 99%

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Blanco

Alečković

Hua

et al. 2011

Journal of Biological Chemistry

114

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Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis.Metastasis is responsible for the majority of cancer-related deaths (1). An increasing number of genes have been implicated in mediating different steps of metastasis, but relatively few are mechanistically well characterized (2). One recently verified mediator of distant metastasis is Metadherin (MTDH 3 ; also called Lyric and AEG1 (3-5)). MTDH has been shown to be a key functional target of the 8q22 genomic gain that is frequently observed in poor prognosis breast cancer patients (6). Beyond promoting experimental lung metastasis (3, 6), multiple studies have implicated MTDH as a mediator of several cancer-related processes, such as oncogenesis and angiogenesis (7,8), invasion (9), chemoresistance (6, 10 -12), apoptosis resistance (13), and autophagy (14). Despite the abundance of MTDH phenotypes, a consensus understanding of its underlying molecular mechanisms has not yet been reached. MTDH has been shown to influence several oncogenic signaling pathways and transcription factors, such as Ha-Ras (15), PI3K/AKT (13), ERK, Wnt/␤-catenin (8), NF-B (16), c-Myc (15), and FOXO1/FOXO3a (17, 18). However, MTDH regulation of signaling pathways appears to be context-dependent with affected pathways varying by tumor type and cell line (19,20). Furthermore, prior work on MTDH molecular mechanisms has largely focused on hypothesis-driven investigations into the ability of MTDH to influence classical oncogenic pathways with little exploration to date on protein-level interactions (16,21).In this study, we aimed to expand the knowledge of MTDH molecular functionality and also uncover novel genes involved in promoting distant metastasis. Our approach utilized an unbiased, mass spectrometry-based screen for MTDH-interacting partners. We identified and characterized the interaction between MTDH and one such protein, SND1. SND1 is a multifunctional protein with reported roles in transcriptional activation (22), RNA editing (23, 24), formation of the RNAinduced ...

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“…59 To complete the 3D model of the protein, each of the SN1-4 domains can be reliably reconstructed based on the available crystal structures of staphylococcal nuclease (PDB 1SNC) and human SN5 (PDB 2O4X), for example, the SN2 domain of spruce TSN shown in Figure 2c. The analysis of the metacaspase mcII-Pa cleavage sites in this model reveals that all of them are located in loop regions: three in the loops situated between SN1-4 domains and one in the middle of a structured but solvent accessible loop (a2-b8) of the SN2 domain (Figure 2c).…”

Section: In Vivo Metacaspase Degradome: Tudor Staphylococcal Nucleasementioning

confidence: 99%

Metacaspases

et al. 2011

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Metacaspases are cysteine-dependent proteases found in protozoa, fungi and plants and are distantly related to metazoan caspases. Although metacaspases share structural properties with those of caspases, they lack Asp specificity and cleave their targets after Arg or Lys residues. Studies performed over the past 10 years have demonstrated that metacaspases are multifunctional proteases essential for normal physiology of non-metazoan organisms. This article provides a comprehensive overview of the metacaspase function and molecular regulation during programmed cell death, stress and cell proliferation, as well as an analysis of the first metacaspase-mediated proteolytic pathway. To prevent further misapplication of caspase-specific molecular probes for measuring and inhibiting metacaspase activity, we provide a list of probes suitable for metacaspases.

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The multifunctional human p100 protein 'hooks' methylated ligands

Cited by 74 publications

References 37 publications

Synaptotagmin 11 interacts with components of the RNA‐induced silencing complex RISC in clonal pancreatic β‐cells

Synaptotagmin 11 interacts with components of the RNA‐induced silencing complex RISC in clonal pancreatic β‐cells

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Metacaspases

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