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Small nucleolar RNP scleroderma autoantigens associate with phosphorylated serine/arginine splicing factors during
K Overzet1, T J Gensler, S J Kim
1Denver Arthritis Clinic, Colorado, USA.
Arthritis and Rheumatism
|June 17, 2000
Summary
Scleroderma autoantigens, small nucleolar RNPs (snoRNPs), associate with phosphoproteins during apoptosis. This association, involving serine/arginine splicing factors, may link scleroderma autoimmunity to cell death pathways or mercury exposure.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Stress Response
Background:
- Autoantibodies targeting phosphorylated proteins are common in systemic lupus erythematosus.
- Scleroderma autoantigens, such as small nucleolar RNPs (snoRNPs), are implicated in autoimmune responses.
Purpose of the Study:
- To investigate the association of scleroderma autoantigens (snoRNPs) with phosphoproteins under cellular stress.
- To determine if this association is linked to apoptotic pathways.
Main Methods:
- Screening monoclonal antibodies from mercury-exposed mice against phosphoproteins in stressed Jurkat T cells.
- Utilizing radiolabeled cell lysates to identify protein complexes.
Main Results:
- SnoRNPs precipitated a phosphoprotein complex (pp42, pp34, pp23) from apoptotic cells, including novel phosphoproteins (pp62, pp18).
- Phosphorylation and recruitment of these proteins to snoRNPs were induced by various apoptotic stimuli and blocked by Bcl-2.
- No association was observed with mercury treatment; the complex included serine/arginine splicing factors (SRp40).
Conclusions:
- The association of phosphorylated SR proteins with snoRNPs during apoptosis suggests a link to scleroderma autoimmunity.
- This immune response may be triggered by apoptotic stimuli or mercury exposure.