The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC–Cdc20 complex

Song, Min Sup; Song, Su Jeong; Ayad, Nagi G.; Chang, Jeong-In; Lee, Juhyun; Hong, Hyun Kyung; Lee, Ho; Choi, Naeyun; Kim, Young Tae; Kim, Hojoong; Kim, Jin Woo; Choi, Eui Ju; Kirschner, Marc W.; Lim, Dae–Sik

doi:10.1038/ncb1091

Cited by 289 publications

(348 citation statements)

References 29 publications

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“…The tumor suppressor RASSF1A is degraded at the G 1 -S transition Previous studies have suggested a growth-inhibitory function of RASSF1A at G 1 (Shivakumar et al, 2002;Rong et al, 2004) and during mitosis (Song et al, 2004;Vos et al, 2004). Thus, we reexamined the ability of RASSF1A to affect the cell cycle progression in various cell lines (U2OS, SaoS2, H1299, A549, MCF7, HeLa and 293T).…”

Section: Resultsmentioning

confidence: 99%

“…RASSF1A regulates the mitotic progression, microtubule dynamics (Song et al, 2004;Vos et al, 2004) and G 1 -S transition (Fenton et al, 2004). The frequently observed downregulation of RASSF1A expression in human tumors has in many cases been attributed to promoter methylation (Agathanggelou et al, 2005), however, other potential causes have not been revealed yet.…”

Section: Discussionmentioning

confidence: 99%

“…Given that RASSF1A has a tumor suppressor function by inhibiting cell proliferation and survival (Dammann et al, 2000;Shivakumar et al, 2002;Song et al, 2004;Baksh et al, 2005), we thus examined whether Skp2 inhibits the tumor suppression function of RASSF1A. Overexpression of wild-type and S203A mutant forms of RASSF1A resulted in a significant loss of viability in U2OS cells (Figures 6a and b).…”

Section: Skp2 Regulates the Antiproliferative And Antisurvival Functimentioning

confidence: 99%

“…The vectors for HA-RASSF1A, GST-RASSF1A and retroviral RASSF1A plasmid were previously described (Song et al, 2004). The plasmids pcDNA3-Flag or -Myc-Skp2 and -Flag or -Myc-Skp2(DF) were kindly provided by M Pagano, and plasmids encoding other F-box proteins were kindly provided by JW Harper.…”

Section: Plasmids and Protein Generationmentioning

confidence: 99%

“…RASSF1A has been shown to regulate mitotic progression by inhibiting the activity of APCCdc20 (Song et al, 2004) and affect microtubule dynamics (Vos et al, 2004). It binds the p120 E4F transcription factor that forms a complex with both the Rb and p53 tumor suppressors (Fenton et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1–S transition

Song

Kim

et al. 2007

Oncogene

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The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G 1 -S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser 203 to alanine results in a delay in cell cycle progression from G 1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G 1 -S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Skp2 Regulates the Antiproliferative And Antisurvival Functimentioning

confidence: 99%

Section: Plasmids and Protein Generationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1–S transition

Song

Kim

et al. 2007

Oncogene

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Blind men and elephants: What do citation summaries tell us about a research article?

Elkiss

Shen

Fader

et al. 2007

J. Am. Soc. Inf. Sci.

145

115

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The old Asian legend about the blind men and the elephant comes to mind when looking at how different authors of scientific papers describe a piece of related prior work. It turns out that different citations to the same paper often focus on different aspects of that paper and that neither provides a full description of its full set of contributions. In this article, we will describe our investigation of this phenomenon. We studied citation summaries in the context of research papers in the biomedical domain. A citation summary is the set of citing sentences for a given article and can be used as a surrogate for the actual article in a variety of scenarios. It contains information that was deemed by peers to be important. Our study shows that citation summaries overlap to some extent with the abstracts of the papers and that they also differ from them in that they focus on different aspects of these papers than do the abstracts. In addition to this, co-cited articles (which are pairs of articles cited by another article) tend to be similar. We show results based on a lexical similarity metric called cohesion to justify our claims.

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Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

Charaniya

Karypis²,

2009

Biotech & Bioengineering

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In the past decade we have witnessed a drastic increase in the productivity of mammalian cell culture-based processes. High-producing cell lines that synthesize and secrete these therapeutics have contributed largely to the advances in process development. To elucidate the productivity trait in the context of physiological functions, the transcriptomes of several NS0 cell lines with a wide range of antibody productivity were compared. Gene set testing (GST) analysis was used to identify pathways and biological functions that are altered in high producers. Three complementary tools for GST-gene set enrichment analysis (GSEA), gene set analysis (GSA), and MAPPFinder, were used to identify groups of functionally coherent genes that are up- or downregulated in high producers. Major functional classes identified include those involved in protein processing and transport, such as protein modification, vesicle trafficking, and protein turnover. A significant proportion of genes involved in mitochondrial ribosomal function, cell cycle regulation, cytoskeleton-related elements are also differentially altered in high producers. The observed correlation of these functional classes with productivity suggests that simultaneous modulation of several physiological functions is a potential route to high productivity.

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The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC–Cdc20 complex

Cited by 289 publications

References 29 publications

Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1–S transition

Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1–S transition

Blind men and elephants: What do citation summaries tell us about a research article?

Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

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