<i>p53</i> is a regulator of the metastasis suppressor gene <i>Nm23‐H1</i>

Chen, Shen Liang; Wu, Yi; Shieh, Hsin Ying; Yen, Chun Che; Shen, Jui-Lung; Lin, Kwang Huei

doi:10.1002/mc.10110

Cited by 31 publications

(20 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nm23-H1 that encodes nucleoside diphosphate kinase (NDPK-A) is up-regulated at the mRNA and protein level upon activation of wild-type p53 (29). It is a negative regulator of cell proliferation and its expression is reduced in metastatic human tumors including melanoma and breast carcinoma.…”

Section: Relationship Between Protein Expression Changes and Apoptosismentioning

confidence: 99%

p53 targets identified by protein expression profiling

Rahman-Roblick

Roblick

Hellman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

p53 triggers cell cycle arrest and apoptosis through transcriptional regulation of specific target genes. We have investigated the effect of p53 activation on the proteome using 2D gel electrophoresis analysis of mitomycin C-treated HCT116 colon carcinoma cells carrying wild-type p53. Approximately 5,800 protein spots were separated in overlapping narrow-pH-range gel strips, and 115 protein spots showed significant expression changes upon p53 activation. The identity of 55 protein spots was obtained by mass spectrometry. The majority of the identified proteins have no previous connection to p53. The proteins fall into different functional categories, such as mRNA processing, translation, redox regulation, and apoptosis, consistent with the idea that p53 regulates multiple cellular pathways. p53-dependent regulation of five of the up-regulated proteins, eIF5A, hnRNP C1/C2, hnRNP K, lamin A/C, and Nm23-H1, and two of the down-regulated proteins, Prx II and TrpRS, was examined in further detail. Analysis of mRNA expression levels demonstrated both transcription-dependent and transcription-independent regulation among the identified targets. Thus, this study reveals protein targets of p53 and highlights the role of transcription-independent effects for the p53-induced biological response.proteomics ͉ transcription factor ͉ cancer

show abstract

Section: Relationship Between Protein Expression Changes and Apoptosismentioning

confidence: 99%

p53 targets identified by protein expression profiling

Rahman-Roblick

Roblick

Hellman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This kinase is activated by various cellular stresses and mediates immediate-early gene expression in response to such stimuli. JNK1 is also important for UV-induced phosphorylation of p53 and p53-mediated apoptosis (Chen et al, 2003;Liu et al, 2004). It is thus plausible that JNK1 is responsible for p53-dependent phosphorylation of specific proteins, including the proteins identified here.…”

mentioning

confidence: 66%

“…The Nm23 metastasis inhibition factor was also previously shown by us and others to be upregulated by p53, at both the RNA and protein level (Chen et al, 2003;Rahman-Roblick et al, 2007). Mutation in the Nm23-H1 gene is associated with metastasis in colorectal cancer (Wang et al, 1993).…”

mentioning

confidence: 68%

Proteomic identification of p53-dependent protein phosphorylation

et al. 2008

View full text Add to dashboard Cite

The p53 tumor suppressor regulates transcription of target genes. We have previously analysed the p53-dependent proteome and identified novel protein targets. Here we have examined p53-dependent phosphorylation using two-dimensional gel electrophoresis and staining with the fluorescent phosphoprotein dye Pro-Q Diamond. We report that p53 induces phosphorylation of a subset of proteins including Nm23, DJ-1, ANXA1 and PrxII. Our identification of p53-dependent phosphorylation of specific target proteins reveals new aspects of the p53-dependent cellular response and suggests that such posttranslational modifications may contribute to p53-mediated tumor suppression.

show abstract

“…Tumor suppressor p53, which is involved in the G1 cell cycle check point, regulates NM23 differentially depending on the cell type. p53 upregulates the expression of NM23-H1 at mRNA and protein level in MCF7 and J7B cells; in contrast, p53 downregulates Nm23-H1 in RKO and H1299 cells [52]. Thus, differentiation inhibitory factor NM23 seems to be a key factor in leukemogenesis.…”

Section: Resultsmentioning

confidence: 91%

Proteomics of AML1/ETO Target Proteins: AML1–ETO Targets a C/EBP–NM23 Pathway

et al. 2010

View full text Add to dashboard Cite

Introduction The rational design of targeted therapies for acute myeloid leukemia (AML) requires the discovery of novel protein pathways in the systems biology of a specific AML subtype. We have shown that in the AML subtype with translocation t(8;21), the leukemic fusion protein AML1-ETO inhibits the function of transcription factors PU.1 and C/EBPα via direct protein-protein interaction. In addition, recently using proteomics, we have also shown that the AML subtypes differ in their proteome, interactome, and post-translational modifications. Methods We, therefore, hypothesized that the systematic identification of target proteins of AML1-ETO on a global proteome-wide level will lead to novel insights into the systems biology of t(8;21) AML on a post-genomic functional level. Thus, 6 h after inducible expression of AML1-ETO, protein expression changes were identified by two-dimensional gel electrophoresis and subsequent mass spectrometry analysis. Results Twenty-eight target proteins of AML1-ETO including prohibitin, NM23, HSP27, and Annexin1 were identified by MALDI-TOF mass spectrometry. AML1-ETO upregulated the differentiation inhibitory factor NM23 protein expression after 6 h, and the NM23 mRNA expression was also elevated in t(8;21) AML patient samples in comparison with normal bone marrow. AML1-ETO inhibited the ability of C/EBP transcription factors to downregulate the NM23 promoter. These data suggest a model in which AML1-ETO inhibits the C/EBP-induced downregulation of the NM23 promoter and thereby increases the protein level of differentiation inhibitory factor NM23. Conclusions Proteomic pathway discovery can identify novel functional pathways in AML, such as the AML1-ETO-C/EBP-NM23 pathway, as the main step towards a systems biology and therapy of AML.

show abstract

p53 is a regulator of the metastasis suppressor gene Nm23‐H1

Cited by 31 publications

References 52 publications

p53 targets identified by protein expression profiling

p53 targets identified by protein expression profiling

Proteomic identification of p53-dependent protein phosphorylation

Proteomics of AML1/ETO Target Proteins: AML1–ETO Targets a C/EBP–NM23 Pathway

Contact Info

Product

Resources

About