B-50/growth-associated protein-43, a marker of neural development inXenopus laevis

Schrama, Loes H.; Lepperdinger, Günter; Moritz, Albrecht; Engel, Nathalie; Marquart, Arnoud; Oestreicher, A.B.; Eggen, Bart J. L.; Rage, W.J.; Richter, Klaus; Destrée, Olivier

doi:10.1016/s0306-4522(96)00400-9

Cited by 12 publications

(9 citation statements)

References 74 publications

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“…To confirm this, the induction of growth-associated protein 43 (GAP-43) and p21 was examined by Western blot analysis. GAP-43 is a neuronal differentiation marker whose expression directly correlates with the extent of differentiation, while p21 is required for the cell cycle arrest mediated by NGF during differentiation (14,41). We showed that GAP-43 was induced in an NGF-dependent manner ( Fig.…”

Section: Vol 27 2007mentioning

confidence: 68%

ΔNp73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA

Zhang

Chen

2007

Molecular and Cellular Biology

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p73, a member of the p53 family, expresses two classes of proteins: the full-length TAp73 and the Nterminally truncated ⌬Np73. While TAp73 possesses many p53-like features, ⌬Np73 is dominant negative towards TAp73 and p53 and appears to have distinct functions in tumorigenesis and neuronal development. Given its biological importance, we investigated the role of ⌬Np73 in nerve growth factor (NGF)-mediated neuronal differentiation in PC12 cells. We show that overexpression of ⌬Np73␣ or ⌬Np73␤ inhibits NGFmediated neuronal differentiation in both p53-dependent and -independent manners. In line with this, we showed that the level of endogenous ⌬Np73 is progressively diminished in differentiating PC12 cells upon NGF treatment and knockdown of ⌬Np73 promotes NGF-mediated neuronal differentiation. Interestingly, we found that the ability of ⌬Np73 to suppress NGF-mediated neuronal differentiation is correlated with its ability to regulate the expression of TrkA, the high-affinity NGF receptor. Specifically, we found that ⌬Np73 directly binds to the TrkA promoter and transcriptionally represses TrkA expression, which in turn attenuates the NGF-mediated mitogen-activated protein kinase pathway. Conversely, the steady-state level of TrkA is increased upon knockdown of ⌬Np73. Furthermore, we found that histone deacetylase 1 (HDAC1) and HDAC2 are recruited by ⌬Np73 to the TrkA promoter and act as corepressors to suppress TrkA expression, which can be relieved by trichostatin A, an HDAC inhibitor. Taken together, we conclude that ⌬Np73 negatively regulates NGF-mediated neuronal differentiation by transrepressing TrkA.

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Section: Vol 27 2007mentioning

confidence: 68%

ΔNp73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA

Zhang

Chen

2007

Molecular and Cellular Biology

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“…p21 plays a role in NGF-mediated differentiation by inducing cell cycle arrest in G1 15 whereas GAP-43 is a late differentiation marker associated with neurite outgrowth. 16 As shown in Figure 1I, overexpression of p53 alone induced p21, but not GAP-43 ( Figure 1I, lane 2), which might explain why p53 alone cannot induce PC12 cells to differentiate. Upon NGF treatment, endogenous p53 was accumulated accompanied by the induction of p21 and GAP-43 ( Figure 1I, lane 3).…”

Section: Exogenous P53 Promotes Ngf-mediated Neurite Outgrowth In Pc1mentioning

confidence: 81%

p53 is required for nerve growth factor-mediated differentiation of PC12 cells via regulation of TrkA levels

2006

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Abstractp53 is necessary for the elimination of neural cells inappropriately differentiated or in response to stimuli. However, the role of p53 in neuronal differentiation is not certain. Here, we showed that nerve growth factor (NGF)-mediated differentiation in PC12 cells is enhanced by overexpression of wild-type p53 but inhibited by mutant p53 or knockdown of endogenous wild-type p53, the latter of which can be rescued by expression of exogenous wild-type p53. Interestingly, p53 knockdown or overexpression of mutant p53 attenuates NGF-mediated activation of TrkA, the high-affinity receptor for NGF and a tyrosine kinase, and activation of the mitogen-activated protein kinase pathway. In addition, p53 knockdown reduces the constitutive levels of TrkA, which renders PC12 cells inert to NGF. And finally, we showed that both constitutive and stimuli-induced expressions of TrkA are regulated by p53 and that induction of TrkA by activated endogenous p53 enhances NGFmediated differentiation. Taken together, our data demonstrate that p53 plays a critical role in NGF-mediated neuronal differentiation in PC12 cells at least in part via regulation of TrkA levels.

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“…Anesthetized frogs were perfused with 4% paraformaldehyde and processed for cryosectioning to yield transverse sections with a thickness of 20 m. These sections each contained both sides of the head, as described previously (Gervasi et al, 2003). For immunohistochemistry, primary antibodies (#1-5, mouse monoclonal; #6 -9, rabbit antisera; #10, goat antiserum) were directed against (1) hnRNP K, 1:100 (clone 3C2; Santa Cruz Biotechnology) Liu and Szaro, 2011), (2) Xenopus NF-M, 2 g/ml (RMO270) (Szaro et al, 1989;Wetzel et al, 1989), (3) a Xenopus neuronal-␤-tubulin (N-␤-tubulin) isotype, 1:100 (clone JDR.38B; Sigma-Aldrich) (Moody et al, 1996), (4) GAP-43, 1:500 (clone NM2, Thermo Scientific) (Schrama et al, 1997), (5) proliferating cell nuclear antigen (PCNA), 1:1000 (clone PC10; Sigma-Aldrich) (Gervasi et al, 2000), (6) the conserved carboxy terminal region of tau (tau-3Ј), 1:2000 (Black et al, 1996;Liu and Szaro, 2011), (7) Xenopus peripherin, 1:2000 (Gervasi et al, 2000), (8) Xenopus hnRNP E2, 1:2000 (Gravina et al, 2002), (9) S6 ribosomal protein, 1:100 (#2217, Cell Signaling Technology), and (10) WGA, 1:100 (#AS-2024, Vector Laboratories). 4Ј,6-Diamidino-2-phenylindole (DAPI) and 7-aminoactinomycin D (7-AAD) (10 g/ml in 1 ϫ PBS, Invitrogen) were used to stain cellular nuclei for conventional epifluorescence and confocal laser scanning microscopy (CLSM), respectively.…”

Section: Methodsmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoprotein K, an RNA-Binding Protein, Is Required for Optic Axon Regeneration inXenopus laevis

Liu

Yu²,

Deaton³

et al. 2012

J. Neurosci.

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Axotomized optic axons of Xenopus laevis, in contrast to those of mammals, retain their ability to regenerate throughout life. To better understand the molecular basis for this successful regeneration, we focused on the role of an RNA-binding protein, heterogeneous nuclear ribonucleoprotein (hnRNP) K, because it is required for axonogenesis during development and because several of its RNA targets are under strong post-transcriptional control during regeneration. At 11 d after optic nerve crush, hnRNP K underwent significant translocation into the nucleus of retinal ganglion cells (RGCs), indicating that the protein became activated during regeneration. To suppress its expression, we intravitreously injected an antisense Vivo-Morpholino oligonucleotide targeting hnRNP K. In uninjured eyes, it efficiently knocked down hnRNP K expression in only the RGCs, without inducing either an axotomy response or axon degeneration. After optic nerve crush, staining for multiple markers of regenerating axons showed no regrowth of axons beyond the lesion site with hnRNP K knockdown. RGCs nonetheless responded to the injury by increasing expression of multiple growthassociated RNAs and experienced no additional neurodegeneration above that normally seen with optic nerve injury. At the molecular level, hnRNP K knockdown during regeneration inhibited protein, but not mRNA, expression of several known hnRNP K RNA targets (NF-M, GAP-43) by compromising their efficient nuclear transport and disrupting their loading onto polysomes for translation. Our study therefore provides evidence of a novel post-transcriptional regulatory pathway orchestrated by hnRNP K that is essential for successful CNS axon regeneration.

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B-50/growth-associated protein-43, a marker of neural development inXenopus laevis

Cited by 12 publications

References 74 publications

ΔNp73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA

ΔNp73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA

p53 is required for nerve growth factor-mediated differentiation of PC12 cells via regulation of TrkA levels

Heterogeneous Nuclear Ribonucleoprotein K, an RNA-Binding Protein, Is Required for Optic Axon Regeneration inXenopus laevis

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