Merlin Neutralizes the Inhibitory Effect of Mdm2 on p53*

The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function. The results showed that merlin increased the p53 stability by inhibiting the Mdm2-mediated degradation of p53, which accompanied the increase in the p53-dependent transcriptional activity. The stabilization of p53 by merlin appeared to be accomplished through Mdm2 degradation, and the N-terminal region of merlin was responsible for this novel activity. This study also showed that overexpression of merlin-induced apoptosis of cells depending preferentially on p53 in response to the serum starvation or a chemotherapeutic agent. These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.

• Publication year

  2004

• Venue

  Journal of Biological Chemistry

• Publication date

  2004-02-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M305526200PMID 14679203
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Merlin overexpression induces apoptosis preferentially in a p53-dependent manner under serum starvation or chemotherapeutic treatment.

  Confidence 0.90

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• The stabilization of p53 by merlin appears to occur through Mdm2 degradation, and the N-terminal region of merlin is responsible for this activity.

  Confidence 0.92

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• Merlin-associated stabilization of p53 is accompanied by increased p53-dependent transcriptional activity.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• Merlin increases p53 stability by inhibiting Mdm2-mediated p53 degradation.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review

• apoptosis

  cellular process

  Programmed cell death measured as a cellular response after merlin overexpression in the reported conditions.

  Aliases: programmed cell death

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• mdm2

  protein, enzyme

  An E3 ubiquitin ligase that mediates p53 degradation and is targeted in the merlin-related mechanism described here.

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• mdm2-mediated p53 degradation

  molecular process, regulatory process

  The ubiquitination and proteasome-linked process by which Mdm2 reduces p53 abundance.

  Aliases: Mdm2-dependent p53 degradation

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• merlin

  protein, tumor suppressor

  A neurofibromatosis 2-related tumor suppressor protein analyzed for its effects on p53 regulation.

  Aliases: NF2-related tumor suppressor merlin

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• n-terminal region of merlin

  protein region, domain

  The amino-terminal portion of merlin implicated in the activity described in this abstract.

  Aliases: merlin N-terminus, N-terminus of merlin

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• p53

  protein

  A tumor suppressor protein whose stability and transcriptional activity are examined in relation to merlin and Mdm2.

  Aliases: p53 tumor suppressor

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review
• p53-dependent transcriptional activity

  molecular function, regulatory activity

  Transcriptional output driven by p53 as a downstream readout of p53 activation.

  Aliases: p53 transcriptional activity

  박진우 (dztg5apj7m) extractionB (s683577b42) review폴라포 (zc8cpxex67) reviewq (76h6bfydm6) review

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  2002cited by this paper
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