RGD Reference Report - Activation of the ubiquitin proteolytic system in murine acquired immunodeficiency syndrome affects IkappaBalpha turnover. - Rat Genome Database

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Activation of the ubiquitin proteolytic system in murine acquired immunodeficiency syndrome affects IkappaBalpha turnover.

Authors: Crinelli, R  Bianchi, M  Gentilini, L  Magnani, M  Hiscott, J 
Citation: Crinelli R, etal., Eur J Biochem. 1999 Jul;263(1):202-11. doi: 10.1046/j.1432-1327.1999.00485.x.
RGD ID: 127285021
Pubmed: PMID:10429205   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1432-1327.1999.00485.x   (Journal Full-text)

Murine acquired immunodeficiency syndrome (MAIDS) is a complex immunopathology caused by a defective murine leukemia virus (LP-BM5) that mainly targets B-lymphocytes. Lymphadenophathy, splenomegaly, hypergammaglobulinemia and progressive immunodeficiency are prominent features of MAIDS. Previously, we showed that the ubiquitin proteolytic system was upregulated in infected lymph nodes [Crinelli, R., Fraternale, A., Casabianca, A. & Magnani, M. (1997) Eur. J. Biochem. 247, 91-97]. In this report, we demonstrate that increased 26S proteasome activity is responsible for accelerated turnover of the IkappaBalpha inhibitor in lymph node extracts derived from animals with MAIDS. The molecular mechanisms mediating IkappaBalpha proteolysis involved constitutive phosphorylation of IkappaBalpha at Ser32 and Ser36 and subsequent ubiquitination, suggesting persistent activation of an NF-kappaB inducing pathway. Interestingly, enhanced IkappaBalpha degradation did not result in enhanced NF-kappaB DNA binding activity, but rather in a different subunit composition. The modulation of NF-kappaB/IkappaB system may affect multiple immunoregulatory pathways and may in part explain the mechanisms leading to the profound immune dysregulation involved in MAIDS pathogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NFKBIAHumanMurine Acquired Immunodeficiency Syndrome  ISONfkbia (Mus musculus)protein:decreased expression:lymph node (mouse)RGD 
NfkbiaRatMurine Acquired Immunodeficiency Syndrome  ISONfkbia (Mus musculus)protein:decreased expression:lymph node (mouse)RGD 
NfkbiaMouseMurine Acquired Immunodeficiency Syndrome  IEP protein:decreased expression:lymph node (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfkbia  (NFKB inhibitor alpha)

Genes (Mus musculus)
Nfkbia  (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha)

Genes (Homo sapiens)
NFKBIA  (NFKB inhibitor alpha)


Additional Information