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Mss4 protein is a regulator of stress response and apoptosis

B M Walter1, C Nordhoff, G Varga

  • 1Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Muenster University Hospital, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.

Cell Death & Disease
|April 13, 2012
PubMed

Insights

Mammalian suppressor of Sec4 (Mss4) acts as a protective chaperone, not a typical nucleotide exchange factor. Upregulation of Mss4 during stress inhibits programmed cell death by interacting with eukaryotic translation initiation factor 3 subunit f.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Stress Response

Background:

  • Mss4 (mammalian suppressor of Sec4) is a conserved protein similar to nucleotide exchange factors.
  • Mss4 exhibits low catalytic activity with Rab GTPases, suggesting a chaperone role.
  • Its function as a chaperone protecting Rab GTPases from degradation is proposed.

Purpose of the Study:

  • To provide further evidence for the chaperone-like properties of Mss4.
  • To investigate the regulation of Mss4 expression under stress conditions.
  • To elucidate the mechanism of Mss4-mediated inhibition of apoptosis.

Main Methods:

  • Analysis of Mss4 mRNA and protein levels under various stress stimuli.
  • Investigation of the role of the JNK stress MAPK signaling pathway in Mss4 regulation.
  • Molecular analysis of Mss4 interaction with eIF3f.

Main Results:

  • Cellular Mss4 mRNA and protein levels are rapidly altered by diverse extracellular stress stimuli.
  • Mss4 regulation is primarily mediated by the JNK stress MAPK signaling pathway, similar to heat shock proteins.
  • Upregulation of Mss4 confers protection against programmed cell death.
  • Mss4 inhibits apoptosis through interaction with eIF3f, a pro-apoptotic protein in the translation initiation complex.

Conclusions:

  • Mss4 functions as a stress-inducible chaperone with anti-apoptotic properties.
  • The JNK pathway is crucial for Mss4's stress-induced upregulation.
  • Interaction with eIF3f is the key mechanism for Mss4's protective role against apoptosis.

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