PMID- 10429205
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 263
IP  - 1
DP  - 1999 Jul
TI  - Activation of the ubiquitin proteolytic system in murine acquired
      immunodeficiency syndrome affects IkappaBalpha turnover.
PG  - 202-11
AB  - 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.
FAU - Crinelli, R
AU  - Crinelli R
AD  - Instuto di Chimica Biologica 'G. Fornaini', University of Urbino, Italy.
FAU - Bianchi, M
AU  - Bianchi M
FAU - Gentilini, L
AU  - Gentilini L
FAU - Magnani, M
AU  - Magnani M
FAU - Hiscott, J
AU  - Hiscott J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Ubiquitins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
SB  - X
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA/metabolism
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Endopeptidases/*metabolism
MH  - Enzyme Activation
MH  - Female
MH  - I-kappa B Kinase
MH  - *I-kappa B Proteins
MH  - Lymph Nodes/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multienzyme Complexes/metabolism
MH  - Murine Acquired Immunodeficiency Syndrome/enzymology/immunology/*metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Proteasome Endopeptidase Complex
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Ubiquitins/*metabolism
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - ejb485 [pii]
AID - 10.1046/j.1432-1327.1999.00485.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Jul;263(1):202-11. doi: 10.1046/j.1432-1327.1999.00485.x.