NucPred—Predicting nuclear localization of proteins

Brameier, Markus; Krings, Andrea; MacCallum, Robert M.

doi:10.1093/bioinformatics/btm066

Cited by 310 publications

(263 citation statements)

References 10 publications

(17 reference statements)

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“…Further analysis of FAM22A/B protein sequences revealed a bipartite nuclear localization sequence (Arg-805 to Arg-822) encoded by exons 7 of FAM22A and FAM22B. In contrast to native YWHAE protein, which is predominantly cytoplasmic (17), YWHAE-FAM22A/B was predicted to be predominantly nuclear (18)(19)(20). YWHAE-FAM22A/ B nuclear localization was confirmed in ESS1 (Fig.…”

Section: Ywhae-fam22 Maintains 14-3-3 Binding Properties and Shows Abmentioning

confidence: 84%

14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma

Lee

Mariño-Enríquez

et al. 2012

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

232

230

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14-3-3 proteins are ubiquitously expressed regulators of various cellular functions, including proliferation, metabolism, and differentiation, and altered 14-3-3 expression is associated with development and progression of cancer. We report a transforming 14-3-3 oncoprotein, which we identified through conventional cytogenetics and whole-transcriptome sequencing analysis as a highly recurrent genetic mechanism in a clinically aggressive form of uterine sarcoma: high-grade endometrial stromal sarcoma (ESS). The 14-3-3 oncoprotein results from a t (10;17) genomic rearrangement, leading to fusion between 14-3-3ε (YWHAE) and either of two nearly identical FAM22 family members (FAM22A or FAM22B). Expression of YWHAE–FAM22 fusion oncoproteins was demonstrated by immunoblot in t (10;17)-bearing frozen tumor and cell line samples. YWHAE–FAM22 fusion gene knockdowns were performed with shRNAs and siRNAs targeting various FAM22A exons in an t (10;17)-bearing ESS cell line (ESS1): Fusion protein expression was inhibited, with corresponding reduction in cell growth and migration. YWHAE–FAM22 maintains a structurally and functionally intact 14-3-3ε (YWHAE) protein-binding domain, which is directed to the nucleus by a FAM22 nuclear localization sequence. In contrast to classic ESS, harboring JAZF1 genetic fusions, YWHAE–FAM22 ESS display high-grade histologic features, a distinct gene-expression profile, and a more aggressive clinical course. Fluorescence in situ hybridization analysis demonstrated absolute specificity of YWHAE–FAM22A/B genetic rearrangement for high-grade ESS, with no fusions detected in other uterine and nonuterine mesenchymal tumors (55 tumor types, n = 827). These discoveries reveal diagnostically and therapeutically relevant models for characterizing aberrant 14-3-3 oncogenic functions.

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Section: Ywhae-fam22 Maintains 14-3-3 Binding Properties and Shows Abmentioning

confidence: 84%

14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma

Lee

Mariño-Enríquez

et al. 2012

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

232

230

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“…It is uncertain whether these residues function as an nuclear export sequences and it is unknown how RASSF1A enters into the nucleus as it does not seem to have a nuclear localization signal, as determined by the NucPre program at http://www.sbc. su.se/Bmaccallr/nucpred/cgi-bin/single.cgi) (Brameier et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Functional importance of RASSF1A microtubule localization and polymorphisms

2010

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Ras association domain family protein 1A (RASSF1A) is one of the more heavily methylated genes in human cancers. In addition to promoter-specific methylation, RASSF1A polymorphisms have been identified in cancer patients. RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules. Currently, the biological importance of RASSF1A microtubule localization and the functional consequences of RASSF1A polymorphisms is not understood. In this study, we have investigated both RASSF1A microtubule association and polymorphisms. Loss of RASSF1A microtubule association resulted in the nuclear appearance of RASSF1A and the loss of association with a-, c-and b-tubulin. Moreover, the loss of microtubule localization of RASSF1A resulted in enhanced tumorpromoting potential, as determined by a xenograft transplantation model in nude mice. It is surprising that, several RASSF1A polymorphisms also lost the ability to associate with a-, c-and b-tubulin and lost the ability to prevent tumor formation in a xenograft nude mouse model when compared with wild-type RASSF1A. Our results demonstrate a role for RASSF1A microtubule localization in eliciting its tumor suppressor function. In addition, some RASSF1A polymorphisms lack the tumor suppressor function of RASSF1A and, if present in patients, may be tumorigenic.

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“…As with the other four rice DNA glycosylases, DNG701 contains a DNA glycosylase domain immediately followed by an EndIII_4Fe-4S domain, and two putative nuclear localization signals are located at the N terminus of the protein (Fig. S1B) (20). Similar to the four Arabidopsis and other four rice DNA glycosylases, the DNG701 glycosylase domain contains a helix-hairpin-helix motif and a glycine/proline-rich loop with an invariant aspartic acid (GPD) (Fig.…”

Section: Dng701mentioning

confidence: 92%

A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

Ding

Mishra

et al. 2011

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

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DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases actively remove 5-meC to counteract transcriptional gene silencing in a locus-specific manner, and have been suggested to maintain the expression of transposons. However, it is unclear whether plant DNA demethylases can promote the transposition of transposons. Here we report the functional characterization of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed 5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of DNG701 in rice plants led to DNA hypermethylation and reduced expression of the retrotransposon Tos17. Tos17 showed less transposition in calli derived from dng701 knockout mutant seeds compared with that in wild-type calli. Overexpression of DNG701 in both rice calli and transgenic plants substantially reduced DNA methylation levels of Tos17 and enhanced its expression. The overexpression also led to more frequent transposition of Tos17 in calli. Our results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible for the demethylation of Tos17 and this DNA demethylase plays a critical role in promoting Tos17 transposition in rice calli.Oryza sativa | incision activity | Tos17 copy number I n eukaryotes, DNA cytosine methylation at carbon 5 of the pyrimidine ring [5-methylcytosine (5-meC)] is an important epigenetic mark that contributes to gene silencing and plays critical roles in development and genome defense against viruses, transposons, and transgenes (1-3). Heavy cytosine methylation usually occurs at heterochromatin and at regions rich in transposons and repetitive DNA (2, 4). Cytosine methylation of DNA, however, is reversible through demethylation (5, 6). DNA demethylation can be passive or active, and active DNA demethylation is catalyzed by one or more enzymes to remove methylated cytosines and can occur independently of DNA replication (7,8). So far, several models have been proposed to explain mechanisms of DNA demethylation in animals (7,8). One of the models suggests that active DNA demethylation is mediated at least in part by a base excision repair (BER) pathway where the AID/Apobec family of deaminases convert 5-meC to T followed by G/T mismatch repair through the DNA glycosylase MBD4 or TDG with the involvement of Gadd45a (7-9). Recently, a new study suggested that 5-meC hydroxylase TET1 promotes DNA demethylation in mammalian cells through a process that requires the BER pathway (10). Nevertheless, many aspects of these models have not been confirmed, and how DNA demethylation is carried out in animals remains controversial (7,8).In contrast to the uncertainty about the mechanism of DNA demethylation in animals, mechanisms of DNA demethylation in plants are much clearer and widely accepted. In the model plant Arabidopsis, research showed that the 5-meC DNA glycosylase/ lyase-me...

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NucPred—Predicting nuclear localization of proteins

Cited by 310 publications

References 10 publications

14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma

14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma

Functional importance of RASSF1A microtubule localization and polymorphisms

A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

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