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The La (SS-B) autoantigen, a key protein in RNA biogenesis, is dephosphorylated and cleaved early during apoptosis

S A Rutjes1, P J Utz, A van der Heijden

  • 1Department of Biochemistry, University of Nijmegen, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.

Cell Death and Differentiation
|November 11, 1999
PubMed

Insights

Apoptosis rapidly dephosphorylates and cleaves the La protein, an autoantigen. These changes, requiring caspase activation, may influence autoantibody production in autoimmune diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis, or programmed cell death, plays a role in autoimmune disease development.
  • Several cellular proteins modified during apoptosis are identified as autoantigens.
  • The La protein's modification during apoptosis requires further investigation.

Purpose of the Study:

  • To investigate the effects of apoptosis on the La protein.
  • To determine if La protein undergoes dephosphorylation and/or cleavage during apoptosis.
  • To elucidate the mechanisms and significance of La protein modifications in apoptosis.

Main Methods:

  • Induction of apoptosis using various initiators in different cell types.
  • Analysis of La protein dephosphorylation and proteolytic cleavage.
  • Inhibition studies using ZnSO4, tetrapeptide caspase inhibitors, and okadaic acid.
  • Mass spectrometry to identify cleavage sites.

Main Results:

  • The La protein is rapidly dephosphorylated upon induction of apoptosis across multiple cell types.
  • A 45 kDa fragment of the La protein is generated through in vivo proteolytic cleavage.
  • Both dephosphorylation and cleavage are inhibited by caspase inhibitors and ZnSO4, indicating caspase involvement.
  • Dephosphorylation is sensitive to okadaic acid, suggesting a role for PP2A-like phosphatases.
  • Cleavage likely occurs at amino acids 371 and/or 374.

Conclusions:

  • Apoptosis induces significant post-translational modifications of the La protein, including dephosphorylation and cleavage.
  • These modifications are mediated by caspases and potentially PP2A-like phosphatases.
  • The observed apoptotic changes in the La protein may be relevant to autoantibody production in autoimmune diseases.

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