The Postmitotic Growth Suppressor Necdin Interacts with a Calcium-binding Protein (NEFA) in Neuronal Cytoplasm

Taniguchi, Naoko; Taniura, Hideo; Niinobe, Michio; Takayama, Chitoshi; Tominaga-Yoshino, Keiko; Ogura, Akihiko; Yoshikawa, Kunio

doi:10.1074/jbc.m005103200

Cited by 83 publications

(75 citation statements)

References 33 publications

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“…NUCB2 is a Ca 2+ binding protein, which also contains putative DNA binding domain, two helix -loop -helix motifs, EF-hands and leucine zipper (Barnikol-Watanabe et al, 1994;Kroll et al, 1999). It interacts with the postmitotic growth suppressor necdin and is proposed to be involved in the regulation of survival and death of postmitotic cells by controlling Ca 2+ homeostasis in the cytoplasm (Taniguchi et al, 2000). Taken together, NUCB2 shows some characteristics of tumour suppressor gene but further studies investigating the functional significance of the 3-nucleotide deletion and downregulation of NUCB2 expression are required.…”

Section: Discussionmentioning

confidence: 99%

Serological identification and expression analysis of gastric cancer-associated genes

et al. 2002

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Serological identification of tumour antigens by recombinant expression cloning has proved to be an effective strategy for the identification of cancer-associated genes having a relevance to cancer aetiology and progression, and for defining possible targets for immunotherapeutic intervention. In the present study we applied this technique to identify immunogenic proteins for gastric cancer that resulted in isolation of 14 distinct serum-reactive antigens. In order to evaluate their role in tumourigenesis and assess the immunogenicity of the identified antigens, we characterised each cDNA clone by DNA sequence analysis, mRNA tissue distribution, comparison of mRNA levels in cancerous and adjacent non-cancerous tissues and the frequency of antibody responses in allogeneic patient and control sera. Previously unknown splice variants of TACC1 and an uncharacterised gene Ga50 were identified. The expression of a newly identified TACC1 isoform is restricted to brain and gastric cancer tissues. Comparison of mRNA levels by semi-quantitative RT -PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1 -an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development. An unusual DNA polymorphism -a three-nucleotide deletion was found in NUCB2 cDNA but its mRNA level was consistently decreased in gastric tumours compared with that in the adjacent noncancerous tissues. This study has revealed several new gastric cancer candidate genes; additional studies are required to gain a deeper insight into their role in the tumorigenesis and their potential as therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Serological identification and expression analysis of gastric cancer-associated genes

et al. 2002

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“…Moreover, necdin is upregulated during neuronal differentiation and is thought to play a role in cell cycle arrest in terminally differentiated neurons [20,23]. Necdin has been described as a transcriptional repressor to interact with and suppress functions of various cytoplasmic and nuclear proteins such as E2F1, p53, hnRNP U and NEFA [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Negative regulation of hypoxia inducible factor‐1α by necdin

Moon

Ahn²,

Park

et al. 2005

FEBS Letters

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Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that mediates cellular and systemic homeostatic responses to reduce O 2 availability, such as erythropoiesis, angiogenesis, and glycolysis. Using the yeast two-hybrid screening system, we found that the oxygen dependent degradation (ODD) domain of HIF-1a interacts with necdin, a growth suppressor. The interaction of necdin with HIF-1a was confirmed using coimmunoprecipitation with the overexpressed HIF-1a. Biological effect of necdin on HIF-1a showed that necdin reduces the transcriptional activity of HIF-1 under hypoxia. Moreover, necdin decreased the level of the HIF-1a protein, but not that of mRNA, implying a possibility of necdin-mediated HIF-1a degradation. Furthermore, necdin has an anti-angiogenic activity in the tube formation assay and CAM assay, which might be due to the downregulation of HIF-1a. Collectively, these results suggest that necdin can be a novel negative regulator of HIF-1a stability via the direct interaction.

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“…CGNs were homogenized with a lysis buffer containing 50 mM Tris-HCl, pH 8.0, 150 mM NaCl, 1% Nonidet P-40, 1 mM EDTA, and the Complete protease inhibitor mixture (Roche) and centrifuged to obtain the supernatant. Cytoplasmic and nuclear soluble fractions were prepared from CGNs as described previously (Taniguchi et al, 2000). Embryonal carcinoma P19 cells were induced to differentiate into neurons as described previously (McBurney et al, 1988).…”

Section: Methodsmentioning

confidence: 99%

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Kurita

Kuwajima²,

Nishimura³

et al. 2006

J. Neurosci.

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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.

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The Postmitotic Growth Suppressor Necdin Interacts with a Calcium-binding Protein (NEFA) in Neuronal Cytoplasm

Cited by 83 publications

References 33 publications

Serological identification and expression analysis of gastric cancer-associated genes

Serological identification and expression analysis of gastric cancer-associated genes

Negative regulation of hypoxia inducible factor‐1α by necdin

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

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