Necdin-related MAGE Proteins Differentially Interact with the E2F1 Transcription Factor and the p75 Neurotrophin Receptor

Kuwako, Ken-ichiro; Taniura, Hideo; Yoshikawa, Kunio

doi:10.1074/jbc.m308454200

Cited by 92 publications

(124 citation statements)

References 47 publications

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“…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: 91%

“…Thus, it is likely that MAGE family proteins with functional similarities to necdin compensate the abnormalities caused by necdin deficiency. Among these necdin-related MAGE proteins, necdin-like 2 (also known as MAGE-G1) is a strong candidate that compensates the deficiency because it interacts with E2F1 and suppresses E2F1-dependent apoptosis (Kuwako et al, 2004). However, little is known about the expression and function of necdin-related MAGE proteins in specific neurons.…”

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 99%

“…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%

“…Necdin, like Rb, targets E2F1 and represses E2F1-dependent transcription in osteosarcoma cells Kuwako et al, 2004). Ectopic expression of necdin inhibits E2F1-induced apoptosis of differentiated neuroblastoma cells (Kobayashi et al, 2002;Kuwako et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 91%

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 99%

Section: Both Cdc2 Expression and Apoptosis Are Increased In Necdindementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Kurita

Kuwajima²,

Nishimura³

et al. 2006

J. Neurosci.

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“…Interestingly, Nse3 shows homology to human MAGE-G1 (also called NDNL2), a protein that contains a melanoma antigen-encoding gene (MAGE) domain. Whereas the function of this family is currently unknown, NDNL2 suppresses cell growth when ectopically expressed and binds to the transcription factor E2F1 (Kuwako et al, 2004). Nse3 also shares homology with the uncharacterized essential Saccharomyces cerevisiae protein YDR288W.…”

mentioning

confidence: 99%

Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

Pébernard

McDonald

Pavlova

et al. 2004

MBoC

112

150

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The structural maintenance of chromosomes (SMC) family of proteins play key roles in the organization, packaging, and repair of chromosomes. Cohesin (Smc1؉3) holds replicated sister chromatids together until mitosis, condensin (Smc2؉4) acts in chromosome condensation, and Smc5؉6 performs currently enigmatic roles in DNA repair and chromatin structure. The SMC heterodimers must associate with non-SMC subunits to perform their functions. Using both biochemical and genetic methods, we have isolated a novel subunit of the Smc5؉6 complex, Nse3. Nse3 is an essential nuclear protein that is required for normal mitotic chromosome segregation and cellular resistance to a number of genotoxic agents. Epistasis with Rhp51 (Rad51) suggests that like Smc5؉6, Nse3 functions in the homologous recombination based repair of DNA damage. We previously identified two non-SMC subunits of Smc5؉6 called Nse1 and Nse2. Analysis of nse1-1, nse2-1, and nse3-1 mutants demonstrates that they are crucial for meiosis. The Nse1 mutant displays meiotic DNA segregation and homologous recombination defects. Spore viability is reduced by nse2-1 and nse3-1, without affecting interhomolog recombination. Finally, genetic interactions shared by the nse mutants suggest that the Smc5؉6 complex is important for replication fork stability. INTRODUCTIONBoth endogenous and exogenous agents constantly threaten genomic integrity. The DNA double-strand break (DSB) is a potentially life-threatening lesion for a cell and can occur spontaneously during growth, as part of a programmed event such as meiosis or as the result of exposure to environmental genotoxic agents. Multiple mechanisms exist to repair DSBs, including nonhomologous end joining and homologous recombination (HR) (Paques and Haber, 1999;Symington, 2002). The HR pathway serves to maintain all original genetic information during DSB repair. Many components of that pathway have been identified and characterized (Paques and Haber, 1999;Symington, 2002). HR involves multiple steps. The DSB is first resected to generate a recombinogenic 3Ј overhang that invades a homologous sequence (e.g., sister chromatid), forming a displacement or D-loop. The invasion step is catalyzed by a number of proteins including the Escherichia coli RecA homologue, Rad51. D-loop formation primes repair synthesis, which is followed by resolution of the recombined duplexes and ligation, producing intact duplex DNA molecules (Paques and Haber, 1999;Symington, 2002). The resolution of recombined DNA duplexes can yield products in which there has been reciprocal exchange of flanking markers (crossover) or not. During mitotic growth gene conversion is infrequently accompanied by crossover, whereas during meiosis, crossover recombination is much more prevalent (Paques and Haber, 1999).Efficient DNA repair requires modulation of both local and higher order chromatin structure. Interestingly, the structural maintenance of chromosomes (SMC) proteins have recently been recognized as important players in DNA repair (Hirano, 2002;Jessberger...

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Neurotrophins and Their Receptors

Bothwell

2007

Handbook of Contemporary Neuropharmacology

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A small family of growth factors known as neurotrophins regulates many different aspects of neuronal function. Although neurotrophins are best known for their ability to promote the survival of embryonic neurons, and to promote growth of neuronal axons, during neural development, neurotrophins also are important regulators of plasticity and synaptic function in the adult nervous system. These functions are mediated by four different receptor proteins—TrkA, TrkB, TrkC, and p75 NTR .

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Necdin-related MAGE Proteins Differentially Interact with the E2F1 Transcription Factor and the p75 Neurotrophin Receptor

Cited by 92 publications

References 47 publications

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis

Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

Neurotrophins and Their Receptors

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