PMID- 16512786
OWN - NLM
STAT- MEDLINE
DCOM- 20060608
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 396
IP  - 2
DP  - 2006 Jun 1
TI  - Intracellular HIV-1 Tat protein represses constitutive LMP2 transcription 
      increasing proteasome activity by interfering with the binding of IRF-1 to STAT1.
PG  - 371-80
AB  - The Tat protein is the transcriptional activator of HIV-1 gene expression, which 
      is not only essential for viral replication, but also important in the complex 
      HIV-induced pathogenesis of AIDS, as both an intracellular and an extracellular 
      released protein. Accordingly, Tat is able to profoundly affect cellular gene 
      expression, regulating several cellular functions, also in non-infected cells. We 
      showed recently that Tat induces modification of immunoproteasomes in that it 
      up-regulates LMP7 (low-molecular-mass polypeptide 7) and MECL1 (multicatalytic 
      endopeptidase complex-like 1) subunits and down-modulates the LMP2 subunit, 
      resulting in a change in the generation and presentation of epitopes in the 
      context of MHC class I. In particular, Tat increases presentation of subdominant 
      and cryptic epitopes. In the present study, we investigated the molecular 
      mechanism responsible for the Tat-induced LMP2 down-regulation and show that 
      intracellular Tat represses transcription of the LMP2 gene by competing with 
      STAT1 (signal transducer and activator of transcription 1) for binding to IRF-1 
      (interferon-regulatory factor-1) on the overlapping ICS-2 (interferon consensus 
      sequence-2)-GAS (gamma-interferon-activated sequence) present in the LMP2 
      promoter. This element is constitutively occupied in vivo by the unphosphorylated 
      STAT1-IRF-1 complex, which is responsible for the basal transcription of the 
      gene. Sequestration of IRF-1 by intracellular Tat impairs the formation of the 
      complex resulting in lower LMP2 gene transcription and LMP2 protein expression, 
      which is associated with increased proteolytic activity. On the other hand, 
      extracellular Tat induces the expression of LMP2. These effects of Tat provide 
      another effective mechanism by which HIV-1 affects antigen presentation in the 
      context of the MHC class I complex and may have important implications in the use 
      of Tat for vaccination strategies.
FAU - Remoli, Anna L
AU  - Remoli AL
AD  - Department of Infectious, Parasitic and Immunomediated Diseases, Istituto 
      Superiore di Sanita, Viale Regina Elena, 299-Rome 00161, Italy.
FAU - Marsili, Giulia
AU  - Marsili G
FAU - Perrotti, Edvige
AU  - Perrotti E
FAU - Gallerani, Eleonora
AU  - Gallerani E
FAU - Ilari, Ramona
AU  - Ilari R
FAU - Nappi, Filomena
AU  - Nappi F
FAU - Cafaro, Aurelio
AU  - Cafaro A
FAU - Ensoli, Barbara
AU  - Ensoli B
FAU - Gavioli, Riccardo
AU  - Gavioli R
FAU - Battistini, Angela
AU  - Battistini A
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Gene Products, tat)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (STAT1 Transcription Factor)
RN  - 144416-78-4 (LMP-2 protein)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
CIN - Biochem J. 2006 Jun 1;396(2):e13-5. PMID: 16703666
MH  - Cysteine Endopeptidases/genetics/*metabolism
MH  - *Enzyme Repression
MH  - Gene Expression Regulation
MH  - Gene Products, tat/genetics/*metabolism/*pharmacology
MH  - Humans
MH  - Interferon Regulatory Factor-1/antagonists & inhibitors/genetics/*metabolism
MH  - Interferon-gamma/metabolism
MH  - Jurkat Cells
MH  - Models, Biological
MH  - Multienzyme Complexes/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Proteasome Endopeptidase Complex/genetics/*metabolism
MH  - Protein Binding
MH  - STAT1 Transcription Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Time Factors
MH  - *Transcription, Genetic
MH  - Transfection
PMC - PMC1462712
EDAT- 2006/03/04 09:00
MHDA- 2006/06/09 09:00
PMCR- 2006/12/01
CRDT- 2006/03/04 09:00
PHST- 2006/03/04 09:00 [pubmed]
PHST- 2006/06/09 09:00 [medline]
PHST- 2006/03/04 09:00 [entrez]
PHST- 2006/12/01 00:00 [pmc-release]
AID - BJ20051570 [pii]
AID - bj3960371 [pii]
AID - 10.1042/BJ20051570 [doi]
PST - ppublish
SO  - Biochem J. 2006 Jun 1;396(2):371-80. doi: 10.1042/BJ20051570.