Stabilization of MyoD by Direct Binding to p57Kip2

Reynaud, Emmanuel G.; Leibovitch, Marie-Pierre; Tintignac, Lionel; Pelpel, Karine; Guillier, Martine; Leibovitch, Serge A.

doi:10.1074/jbc.m907412199

Cited by 94 publications

(78 citation statements)

References 59 publications

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“…Earlier studies on muscle development have shown that p57Kip2 is involved in the differentiation of skeletal muscle and can interact with the myogenic bHLH factor MyoD. 22 We asked whether p57Kip2 could interact in a similar way with neurogenic bHLH factors. HEK293 cells were transfected with p57Kip2 cDNA conjugated with an hemagglutinin (HA)-tag together with various members of different classes of bHLH proteins, and total cellular extracts were immunoprecipitated with p57Kip2 antibodies.…”

Section: Resultsmentioning

confidence: 99%

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

et al. 2009

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Mammalian central nervous system (CNS) development is a highly organized process involving the precise and coordinated timing of cell-cycle exit, differentiation, survival, and migration. These events require proper expression of pro-neuronal genes but also repression of alternative cell fates and restriction of cell-type-specific gene expression. Here, we show that the cyclindependent kinase (CDK) inhibitor p57Kip2 interacted with pro-neuronal basic helix-loop-helix (bHLH) factors such as Mash1, NeuroD, and Nex/Math2. Increased levels of p57Kip2 inhibited Mash1 transcriptional activity independently of CDK interactions and acted as a direct repressor in transcriptional assays. Proliferating telencephalic neural progenitors co-expressed basal levels of Mash1 and p57Kip2, and endogenous p57Kip2 accumulated transiently in the nuclei of neural stem cells (NSCs) during early stages of astrocyte differentiation mediated by ciliary neurotrophic factor (CNTF), independent of cell-cycle exit and at times when Mash1 expression was still prominent. In accordance with these observations, gain-and loss-of-function studies showed that p57Kip2 repressed neuronal differentiation after mitogen withdrawal, but exerted little or no effect on CNTFmediated astroglial differentiation of NSCs. Our data suggest a novel role for p57Kip2 as a context-dependent repressor of neurogenic transcription factors and telencephalic neuronal differentiation. The development of the mammalian central nervous system (CNS) critically relies on a tight coordination among cell proliferation, survival, migration, and differentiation. 1,2 Proper neuronal differentiation does not only require pro-neuronal genes but also regulated repression of other cell fates, such as glial differentiation. 2 Thus, early neural progenitors preferentially differentiate into neurons and do not respond properly to astrocyte-inducing cytokines, at least in part due to DNA methylation of astrocyte-characteristic genes such as glial fibrillary acidic protein (GFAP). 3,4 In line with these observations, it has been shown that loss of the DNA methyl transferase DNMT1 results in hypomethylation and precocious onset of astrocytic genes at the expense of neurogenesis in early neural precursors. 5 In later progenitors, astrocytic genes become demethylated. 3,4 Transcriptional repression of astrocytic genes and thus the correct numbers of progenitors and neurons at these late events, instead depends on other factors such as the Notch-regulated transcription factor CSL/RBP-Jk and the co-repressors N-CoR and SMRT. 6,7 In addition, neurogenic members of the basic helix-loop-helix (bHLH) family of transcription factors, such as Mash1 and Neurogenin (Ngn) 2, interferes with astrocyte differentiation in multipotent neural progenitors at least in part by sequestering the coactivators CBP/p300 required for astrocyte differentiation. 8 Less is understood regarding a corresponding repression of neuronal differentiation during glial differentiation. Hes transcription factors repress neurogenic ...

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Section: Resultsmentioning

confidence: 99%

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

et al. 2009

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“…MyoD expression is also enhanced upon serum deprivation of C2C12 mesenchymal cells prior to the onset of differentiation (70 -73). Cell cycle regulation of MyoD involves the CDK2/cyclin E-dependent degradation by the ubiquitin/proteasome pathway in late G 1 phase, and MyoD is stabilized by direct association with p57 (70,71). Similar to Runx2, MyoD may influence cell cycle progression by transcriptionally regulating the gene for the CDK inhibitor p21.…”

Section: Discussionmentioning

confidence: 99%

The Bone-specific Expression of Runx2 Oscillates during the Cell Cycle to Support a G1-related Antiproliferative Function in Osteoblasts

Galindo

Pratap

Young

et al. 2005

Journal of Biological Chemistry

225

242

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“…Previous studies indicate that overexpression of one of the interacting proteins can provide valuable insights into the biological effects of such interaction (Reynaud et al, 2000;Bai and Merchant, 2001). So, what happens when the intracellular levels of calreticulin are increased by its overexpression?…”

Section: Discussionmentioning

confidence: 99%

Effects of Calreticulin on Viral Cell-to-Cell Movement

et al. 2005

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Cell-to-cell tobacco mosaic virus movement protein (TMV MP) mediates viral spread between the host cells through plasmodesmata. Although several host factors have been shown to interact with TMV MP, none of them coresides with TMV MP within plasmodesmata. We used affinity purification to isolate a tobacco protein that binds TMV MP and identified it as calreticulin. The interaction between TMV MP and calreticulin was confirmed in vivo and in vitro, and both proteins were shown to share a similar pattern of subcellular localization to plasmodesmata. Elevation of the intracellular levels of calreticulin severely interfered with plasmodesmal targeting of TMV MP, which, instead, was redirected to the microtubular network. Furthermore, in TMV-infected plant tissues overexpressing calreticulin, the inability of TMV MP to reach plasmodesmata substantially impaired cell-to-cell movement of the virus. Collectively, these observations suggest a functional relationship between calreticulin, TMV MP, and viral cell-to-cell movement.Following initial infection (usually by mechanical inoculation), many plant viruses, such as tobacco mosaic virus (TMV), spread from cell to cell through plasmodesmata (for review, see Heinlein, 2002;Waigmann et al., 2004), presumably utilizing the existing cellular pathways of plasmodesmal transport. In the case of TMV, this virus encodes a specific cell-to-cell movement protein (MP), which mediates the transport of the viral genomic RNA through plasmodesmata (Deom et al., 1987). To date, MP has been shown to bind TMV RNA (Citovsky et al., 1990(Citovsky et al., , 1992, associate with the cytoskeleton (Heinlein et al., 1995;McLean et al., 1995;Boyko et al., 2000) and endoplasmic reticulum (ER; Heinlein et al., 1998;Reichel and Beachy, 1999), target to plasmodesmata within plant cell walls (Tomenius et al., 1987;Ding et al., 1992a), increase plasmodesmal permeability (Wolf et al., 1989;Waigmann et al., 1994), and undergo negative regulation by phosphorylation (Citovsky et al., 1993;Waigmann et al., 2000;Trutnyeva et al., 2005). To perform many of these functions, TMV MP most likely cooperates with different cellular factors, some of which, such as cell wall pectin methylesterases (PME; Dorokhov et al., 1999;Chen et al., 2000), microtubules (MTs) and actin filaments (Heinlein et al., 1995;McLean et al., 1995;Boyko et al., 2000), and a RIO protein kinase (Yoshioka et al., 2004), are known, while others remain to be discovered. It would be especially interesting to determine whether cellular proteins exist that not only recognize TMV MP but also coreside with it within plasmodesmata.Using TMV MP as specific ligand in a biochemical purification protocol, we showed that it interacts with plant calreticulin. Calreticulin is a Ca 21 -sequestering protein that is highly conserved between different species, including plants ( Nelson et al., 1997; Borisjuk et al., 1998, and refs. therein;Michalak et al., 1998). Functionally, calreticulin is involved in Ca 21 storage and signaling, chaperone activity, cell ad...

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Stabilization of MyoD by Direct Binding to p57Kip2

Abstract: Kip2 , which is conserved in the Cip/Kip proteins, is implicated in protein-protein interaction and confers a specific regulatory mechanism, outside of their Cdk-inhibitory activity, by which the p57 Kip2 family members positively act on myogenic differentiation.

Cited by 94 publications

References 59 publications

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural stem cells

The Bone-specific Expression of Runx2 Oscillates during the Cell Cycle to Support a G1-related Antiproliferative Function in Osteoblasts

Effects of Calreticulin on Viral Cell-to-Cell Movement

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