Negative regulation of hypoxia inducible factor‐1α by necdin

Moon, Hyo Eun; Ahn, Mee Young; Park, Jeong Ae; Min, Kyung Jin; Kwon, Yoo Wook; Kim, Kyu Won

doi:10.1016/j.febslet.2005.05.072

Cited by 31 publications

(37 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that the augmented apoptosis in the EGL in vivo of necdin-deficient cerebellum is attributable, at least in part, to the deregulation of the E2F1-Cdc2 system at early stages of CGN differentiation. Necdin interacts with various proteins involved in neuronal apoptosis such as p53, hypoxia-inducible factor-1␣, and the neurotrophin receptor p75 Tcherpakov et al, 2002;Kuwako et al, 2004;Moon et al, 2005). Thus, we cannot rule out the possibility that these necdin-interacting molecules other than E2F1-related cell cycle proteins are responsible for the enhanced apoptosis in vivo in the EGL of necdin-deficient mice.…”

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 90%

“…Necdin targets many regulatory proteins that control neuronal life-and-death and differentiation Kobayashi et al, 2002;Tcherpakov et al, 2002;Kuwajima et al, 2004Kuwajima et al, , 2006Kuwako et al, 2004Kuwako et al, , 2005Moon et al, 2005). Thus, necdin might serve as a hub protein in the network of proteinprotein interactions to promote and stabilize neuronal terminal differentiation.…”

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 99%

See 1 more Smart Citation

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Kurita

Kuwajima²,

Nishimura³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

The cell cycle-regulatory transcription factor E2F1 induces apoptosis of postmitotic neurons in developmental and pathological situations. E2F1 transcriptionally activates many proapoptotic genes including the cyclin-dependent protein kinase cell division cycle 2 (Cdc2). Necdin is a potent mitotic suppressor expressed predominantly in postmitotic neurons and interacts with E2F1 to suppress E2F1-mediated gene transcription. The necdin gene NDN is maternally imprinted and expressed only from the paternal allele. Deletion of the paternal NDN is implicated in the pathogenesis of Prader-Willi syndrome, a genomic imprinting-associated neurodevelopmental disorder. Here, we show that paternally expressed necdin represses E2F1-dependent cdc2 gene transcription and attenuates apoptosis of postmitotic neurons. Necdin was abundantly expressed in differentiated cerebellar granule neurons (CGNs). Neuronal activity deprivation elevated the expression of both E2F1 and Cdc2 in primary CGNs prepared from mice at postnatal day 6, whereas the necdin levels remained unchanged. In chromatin immunoprecipitation analysis, endogenous necdin was associated with the cdc2 promoter containing an E2F-binding site in activity-deprived CGNs. After activity deprivation, CGNs underwent apoptosis, which was augmented in those prepared from mice defective in the paternal Ndn allele (Ndn ϩm/Ϫp ). The levels of cdc2 mRNA, protein, and kinase activity were significantly higher in Ndn ϩm/Ϫp CGNs than in wild-type CGNs under activity-deprived conditions. Furthermore, the populations of Cdc2-immunoreactive and apoptotic cells were increased in the cerebellum in vivo of Ndn ϩm/Ϫp mice. These results suggest that endogenous necdin attenuates neuronal apoptosis by suppressing the E2F1-Cdc2 system.

show abstract

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 90%

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 99%

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Kurita

Kuwajima²,

Nishimura³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Three of these genes are of particular interest based on published literatures. Necdin (Ndn) is an imprinted transcription factor on chromosome 7 that has previously been implicated in cellular proliferation, collagen gene expression [25], and regulation of the metastasis-associated gene Hif1a [26,27]. Brd4, on chromosome 17, is a bromodomain-containing protein that associates with chromatin [17].…”

Section: Identification Of Ecm Eqtl Candidate Genesmentioning

confidence: 99%

The Diasporin Pathway: a tumor progression-related transcriptional network that predicts breast cancer survival

Crawford

Walker

Lukes

et al. 2008

Clin Exp Metastasis

View full text Add to dashboard Cite

Microarray expression signature analyses have suggested that extracellular matrix (ECM) gene dysregulation is predictive of metastasis in both mouse mammary tumorigenesis and human breast cancer. We have previously demonstrated that such ECM dysregulation is influenced by hereditary germline-encoded variation. To identify novel metastasis efficiency modifiers, we performed expression QTL (eQTL) mapping in recombinant inbred mice by characterizing genetic loci modulating metastasis-predictive ECM gene expression. Three reproducible eQTLs were observed on chromosomes 7, 17 and 18. Candidate genes were identified by correlation analyses and known associations with metastasis. Seven candidates were identified (Ndn, Pi16, Luc7l, Rrp1b, Brd4, Centd3 and Csf1r). Stable transfection of the highly metastatic Mvt-1 mouse mammary tumor cell line with expression vectors encoding each candidate modulated metastasis-predictive ECM gene expression. Implantation of these cells into mice demonstrated that candidate gene ectopic expression impacts tumor progression. Gene expression analyses facilitated the construction of a transcriptional network that we have termed the 'Diasporin Pathway'. This pathway contains the seven candidates, as well as metastasis-predictive ECM genes and metastasis suppressors. Brd4 and Rrp1b appear to form a central node within this network, which likely is a consequence of their physical interaction with the metastasis efficiency modifier Sipa1. Furthermore, we demonstrate that the microarray gene expression signatures induced by activation of ECM eQTL genes in the Mvt-1 cell line can be used to accurately predict survival in a human breast cancer cohort. These data imply that the Diasporin Pathway may be an important nexus in tumor progression in both mice and humans.

show abstract

“…Adhesion of tumor cells to endothelial cells is proposed to figure heavily in cancer metastasis and is involved in the vasculogenesis associated with tumor progression (Hakomori, 2002;Tei et al, 2002). It has been reported that MAGE-D1 is structurally homologous to necdin, which served as a postmitotic neuron-specific growth suppressor, induced growth arrest (Taniura et al, 1998) and could negatively regulate hypoxia inducible factor 1 α (HIF-1α) stability and angiogenesis (Moon et al, 2005). However, the relationship between MAGE-D1 and tumor cell migration and adhesion to endothelium in response to hypoxic stress has not been previously explored.…”

Section: Introductionmentioning

confidence: 96%

Melanoma-Associated Antigen Family Protein-D1 Regulation of Tumor Cell Migration, Adhesion to Endothelium, and Actin Structures Reorganization in Response to Hypoxic Stress

Shen

Xue

et al. 2007

Cell Communication & Adhesion

View full text Add to dashboard Cite

Melanoma-associated antigen family protein-D1 (MAGE-D1) is a recently identified p75 neurotrophin receptor intracellular binding protein and functions as an adaptor that mediates multiple signaling pathways, including Dlx/Msx-mediated transcription. Here, a new regulatory function for MAGE-D1 in tumor cell motility and adhesion to endothelium is described. MAGE-D1 over-expression suppressed HeLa cell and BEL7402 cell migration, invasion, and adhesion to the monolayer of ECV304 cells. We also report that MAGE-D1 over-expression disrupted actin cytoskeleton rearrangement induced by hypoxia and down-regulated hypoxia inducible factor 1-dependent luciferase gene expression. These findings provide new insight into the ability of MAGE-D1 to suppress the motility and adhesion response of tumor cells by interfering with actin cytoskeleton reorganization and hypoxia inducible factor 1-dependent gene expression.

show abstract

Negative regulation of hypoxia inducible factor‐1α by necdin

Cited by 31 publications

References 29 publications

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

The Diasporin Pathway: a tumor progression-related transcriptional network that predicts breast cancer survival

Melanoma-Associated Antigen Family Protein-D1 Regulation of Tumor Cell Migration, Adhesion to Endothelium, and Actin Structures Reorganization in Response to Hypoxic Stress

Contact Info

Product

Resources

About