Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural and proneural genes

Klisch, Tiemo J.; Souopgui, Jacob; Juergens, Kathrin; Rust, Barbara; Pieler, Tomas; Henningfeld, Kristine A.

doi:10.1016/j.ydbio.2005.12.037

Cited by 27 publications

(18 citation statements)

References 75 publications

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“…However, the studies described here support the conclusion that Mad3 promotes proliferation in cultured GNPs and appears to have overlapping activity with Nmyc. The only previous report indicating a functional role of a Mad family member in processes related to proliferation is a recent study suggesting that Xenopus Mxi1 (Xmxi1) is essential for neurogenesis during embryogenesis (27). However, this study demonstrated that Xmxi1 plays an important role in the formation of the mature neural fate, which is necessary for activation by factors that induce neuronal differentiation, and this activity is not directly related to an active role in cell cycle progression.…”

Section: Discussioncontrasting

confidence: 55%

“…Indeed, the original Mad3 cloning and characterization study demonstrated that overexpression of Mad3 (like that of Mad1) is capable of inhibiting Myc-dependent transformation of rat embryo fibroblasts (22), supporting the model that Mad proteins antagonize Myc function in cell growth and VOL. 27,2007 Mad3 REGULATES GRANULE CELL PROLIFERATION 8185…”

Section: Discussionmentioning

confidence: 99%

“…Thus, an interesting possibility that was recently put forth is that cells in S phase are particularly vulnerable to Myc-induced apoptosis, and expression of Mad3 during this period might orchestrate the selective downregulation of apoptosis-related target genes VOL. 27,2007 Mad3 REGULATES GRANULE CELL PROLIFERATION 8187…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Role of the Mad Family Member Mad3 in Cerebellar Granule Neuron Precursor Proliferation

Yun

Rust

Ishimaru

et al. 2007

Molecular and Cellular Biology

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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A Novel Role of the Mad Family Member Mad3 in Cerebellar Granule Neuron Precursor Proliferation

Yun

Rust

Ishimaru

et al. 2007

Molecular and Cellular Biology

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“…Mxi1 also contains an N-terminal Sin3-interacting domain, which recruits the general co-repressor protein Sin3 and an associated transcriptional repression complex containing histone deacetylases to the transcription regulatory regions of target genes. As a result, the core histones are deacetylated and the transcription of target genes is suppressed [14].Some investigators have shown that Mxi1 inhibits the proliferation of DU145 human prostate cancer cells and U87 glioma cells [11,15]. Mutations and deletions in the Mxi1 coding sequence have been described in patients with prostate cancer, neurofibrosarcoma, and neuroglioma [16,17].In addition, Mxi1-knockout mice exhibit a tumorigenic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Change of MAX Interactor 1 Expression in an Anti-Thy1 Nephritis Model and its Effect on Mesangial Cell Proliferation

Liu

Xie

et al. 2011

Cell Physiol Biochem

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Background/Aims: During the disease process of mesangial proliferative glomerulonephritis, the expression of various factors that influence mesangial proliferation is altered. MAX interactor 1 (Mxi1) antagonizes the transcription factor Myc and is believed to be a tumor suppressor. However, no studies have investigated its effect on mesangial cell proliferation. Methods: To investigate the effect of Mxi1 on renal mesangial cell proliferation, we established a classic rat anti-Thy1 mesangial proliferative glomerulonephritis model. Mesangial proliferation was estimated by immunohistochemical analysis of Ki67. Mxi1 expression at each time point was assessed by real-time RT-PCR and Western blot analyses. Furthermore, we altered the expression level of Mxi1 by a plasmid and siRNA to detect its effect on rat mesangial cell proliferation in vitro. Results: Mxi1 expression decreased significantly during the proliferative period of anti-Thy1 nephritis model and then gradually increased as proliferation declined, indicating that Mxi1 may be linked to mesangial cell proliferation. Upregulation of Mxi1 expression via plasmid transfection in vitro reduced the expression of the positive-acting cell cycle regulatory proteins cyclin B1, cyclin D1, cyclin E, CDC2 and CDK2; significantly reduced mesangial cell proliferation; reduced the percentage of S phase cells; and increased the percentage of G2/M phase cells. Inhibition of Mxi1 expression by siRNA in vitro produced the opposite effects: increased expression of cyclin B1, cyclin D1, cyclin E, CDC2 and CDK2; markedly increased cell proliferation; higher percentage of S phase cells; and dramatically lower percentage of G2/M phase cells. Transcription factor c-myc protein expression showed no obvious difference after Mxi1 plasmid and siRNA transfection. The expressions of cell cycle regulatory proteins mentioned above were negative correlated with Mxi1 expression in anti-Thy1 nephritis model. Conclusion: These results suggest that Mxi1 expression levels were inversely correlated with proliferation in anti-Thy1 nephritis rats and it may influence cell cycle progression and thus the rate of mesangial cell proliferation by regulating the expression of c-myc target cell cycle regulatory proteins.

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“…The neuronal determination factor X-ngnr-1 robustly induced the activation of both CRMP-4 and CRMP-2. The positive regulation of CRMP-2 by X-ngnr-1 is similar to the activation of other panneural genes such as Nrp-1 and NCAM (Klisch et al, 2006). …”

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confidence: 76%

Expression and regulation of Xenopus CRMP-4 in the developing nervous system

Souopgui¹,

Klisch²,

Pieler³

et al. 2007

Int. J. Dev. Biol.

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KEY WORDS: Xenopus, primary neurogenesis, neurogenin, CRMP, NotchThe collapsin response mediator proteins (CRMPs) (also known as TOAD (turned on after division), Ulip (unc-33 like protein) and DRP (dihydropyrimidinase family) are a conserved family of cytosolic phosphoproteins highly expressed in the nervous system (Wang and Strittmatter, 1996). Even though the CRMPs exhibit more than 60% amino acid identity to the amidohydrolase family, they do not possess enzymatic activity (Wang and Strittmatter, 1997).The first CRMP was identified as an intracellular mediator of semaphorin/collapsin growth cone collapse (Goshima et al., 1995). However, numerous studies have demonstrated that the activities of CRMPs are not restricted to this repulsive guidance cue and participate in a broad spectrum of additional activities, with function being dependant on the specific interaction with various protein partners (Arimura et al., 2004). CRMP-2 participates in LPA-induced growth cone collapse and regulates axonogenesis through the binding of tubulin heterodimers (Inagaki et al., 2001;Fukata et al., 2002). CRMP-2 also contributes to the establishment of neuronal polarity through the association with Numb and promoting Numb-mediated endocytosis of the neuronal cell adhesion molecule L1 (Nishimura et al., 2003).Int. J. Dev. Biol. 51: 339-343 (2007) CRMP proteins are also targets of a variety of protein kinases. CRMP-2 and CRMP-4 were identified as brain-specific substrates for glycogen synthase kinase 3 (GSK3) and during growth cone collapse, phosphorylation by Rho-associated kinase inhibits microtubule assembly and Numb-mediated endoyctosis Yoshimura et al., 2005;Cole et al., 2006). Recently, CRMP-2 was identified as a negative regulator of p53 and it has been suggested to play a role in the regulation of proliferation (Llanos et al., 2006;Tahimic et al., 2006). Moreover, the CRMPs may contribute to the pathogenesis of specific neurodegenerative disorders (Charrier et al., 2003).Presently, we describe the expression analysis of CRMP-4, during early Xenopus embryogenesis. CRMP-4 is expressed in the differentiating primary neurons and later expression is maintained throughout the central nervous system and in the eye. Correspondingly, CRMP-4 is positively regulated by X-ngnr-1 and negatively regulated by the Notch pathway. Results and DiscussionXenopus CRMP-4 was identified in a microarray screen aimed at identifying genes induced in dissociated ectodermal explants by the neuronal determination transcription factor, X-ngnr-1. Comparison of the predicted amino acid sequence revealed Xenopus CRMP-4 is 90% identical to the corresponding human and mouse sequences. Lower identity was observed between Xenopus CRMP-2 (75%) and other mammalian CRMP members (71-74%) (Fig. 1). The Cdk5 priming and GSK3 phosphorylation sites identified in the mammalian CRMP-2 are conserved (Uchida et al., 2005;Yoshimura et al., 2005).The expression of CRMP-4 during early Xenopus embryogenesis was investigated by RT-PCR analysis with RNA isolated from var...

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Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural and proneural genes

Cited by 27 publications

References 75 publications

A Novel Role of the Mad Family Member Mad3 in Cerebellar Granule Neuron Precursor Proliferation

A Novel Role of the Mad Family Member Mad3 in Cerebellar Granule Neuron Precursor Proliferation

Change of MAX Interactor 1 Expression in an Anti-Thy1 Nephritis Model and its Effect on Mesangial Cell Proliferation

Expression and regulation of Xenopus CRMP-4 in the developing nervous system

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