Genetic analyses using a mouse cell cycle mutant identifies magoh as a novel gene involved in Cdk regulation

Inaki, Makoto; Kato, Dai; Utsugi, Takahiko; Onoda, Fumitoshi; Hanaoka, Fumio; Murakami, Yasufumi

doi:10.1111/j.1365-2443.2010.01479.x

Cited by 15 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…siRNA knockdown of Magoh in HeLa cells causes G2/M arrest(Kittler et al, 2007; Silver et al, 2010). Moreover, similar to our in vitro findings with MEFs and melanocyte-derived cells, Magoh siRNA treated tsFT210 and FM3A cells show reduced proliferation in culture (Inaki et al, 2011). How might Magoh impact melanoblast division?…”

Section: Discussionsupporting

confidence: 86%

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes

Silver

Leeds

Hwang

et al. 2013

Developmental Biology

View full text Add to dashboard Cite

Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waarden burg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haplo insufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development.

show abstract

Section: Discussionsupporting

confidence: 86%

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes

Silver

Leeds

Hwang

et al. 2013

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…21 On the other hand, Magoh is involved in the regulation of mouse Cdks. 11 Totally, it is possible that RBM8A-depleted human cells in our study also have similar deficiency and G2/M arrest via their alternation. EJC serves as a platform for NMD factors and their various roles in cell cycle progression have been reported.…”

Section: Discussionmentioning

confidence: 93%

Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells

Ishigaki

Nakamura

Tatsuno

et al. 2013

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

RBM8A (Y14) contains an RNA-binding motif and forms a tight heterodimer with Magoh. The heterodimer is known to be a member of the exon junction complex that forms on mRNA before export and it is required for mRNA metabolism processes such as splicing, mRNA export and nonsense-mediated mRNA decay. Recently, deficient cellular proliferation has been observed in RBM8A- or Magoh-depleted cells. These results prompted us to study the role of RBM8A in cell cycle progression of human tumour cells. The depletion of RBM8A in A549 cells resulted in poor cell survival and the accumulation of mitotic cells. After release from G1/S arrest induced by a double thymidine block, the RBM8A-silenced cells could not proceed to the next G1 phase beyond G2/M phase. Finally, the sub-G1 population increased and the apoptosis markers caspases 3/7 were activated. Silenced cells exhibited an increased frequency of multipolar or monopolar centrosomes, which may have caused the observed deficiency in cell cycle progression. Finally, silencing of either RBM8A or Magoh resulted in mutual downregulation of the other protein. These results illustrate that the RBM8A-Magoh mRNA binding complex is required for M phase progression and both proteins may be novel targets for anticancer therapy.

show abstract

“…We found that 314 proteins were in common between the proteomes, suggesting a possible function for these proteins throughout mitosis or cytokinesis (Figure 4 and Table S3) [9]. Proteins unique to the CHO mitotic spindle proteome included known spindle components such as SEPT7 and SEPT9, which are required for stable kinetochore localization of CENP-E [48], PAF1, which regulates Histone 2B and mediates the progression of the cell cycle [49], and MAGOHB, the mago-nashi homolog, which regulates cyclin dependent kinases [50]. Proteins appearing in only the CHO midbody proteome included ECT2 and KIF4A, both of which are critical for cytokinesis completion [51], [52].…”

Section: Resultsmentioning

confidence: 99%

Mitotic Spindle Proteomics in Chinese Hamster Ovary Cells

Bonner

Poole

et al. 2011

PLoS ONE

View full text Add to dashboard Cite

Mitosis is a fundamental process in the development of all organisms. The mitotic spindle guides the cell through mitosis as it mediates the segregation of chromosomes, the orientation of the cleavage furrow, and the progression of cell division. Birth defects and tissue-specific cancers often result from abnormalities in mitotic events. Here, we report a proteomic study of the mitotic spindle from Chinese Hamster Ovary (CHO) cells. Four different isolations of metaphase spindles were subjected to Multi-dimensional Protein Identification Technology (MudPIT) analysis and tandem mass spectrometry. We identified 1155 proteins and used Gene Ontology (GO) analysis to categorize proteins into cellular component groups. We then compared our data to the previously published CHO midbody proteome and identified proteins that are unique to the CHO spindle. Our data represent the first mitotic spindle proteome in CHO cells, which augments the list of mitotic spindle components from mammalian cells.

show abstract

Genetic analyses using a mouse cell cycle mutant identifies magoh as a novel gene involved in Cdk regulation

Cited by 15 publications

References 42 publications

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes

The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes

Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells

Mitotic Spindle Proteomics in Chinese Hamster Ovary Cells

Contact Info

Product

Resources

About