Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P20226 (
TATA-binding protein
)
1,297
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising
TATA-binding protein
(
TBP
) and 13
TBP
-associated factors (TAFs).
TBP
binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by
TBP
and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for
TBP
binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box
mimicry
. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/
TBP
complex, revealing TAF11/TAF13 interaction with the DNA binding surface of
TBP
. We identify a highly conserved C-terminal
TBP
-interaction domain (CTID) in TAF13, which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.
...
PMID:Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID. 2911 74
Human cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65)
422-439
mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65
422-439
and TAF9
134-144
(
TATA-box binding protein
associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). A murine model was used to confirm their antigenicity and ability to induce lupus-like symptoms. HCMVpp65
422-439
induced immune responses with the presence of specific antibodies against HCMVpp65
422-439
and TAF9
134-144
, as well as anti-nuclear and anti-double-stranded (ds)DNA antibodies that are characteristic of SLE. In addition, the majority of HCMVpp65
422-439
and TAF9
134-144
immunized mice developed proteinuria, and their renal pathology revealed glomerulonephritis with typical abnormalities, such as mesangial hypercellularity and immune complex deposition. Immunoglobulin eluted from the glomeruli of HCMVpp65
422-439
immunized mice showed cross-reactivity with TAF9
134-144
and dsDNA. Increased anti-TAF9 antibody activity was also observed in the sera from SLE patients compared with healthy people and disease controls. Molecular
mimicry
between HCMVpp65 peptide and host protein has the potential to drive lupus-like autoimmunity. This proof-of-concept study highlights the mechanisms underlying the link between HCMV infection and the induction of SLE.
...
PMID:Human cytomegalovirus pp65 peptide-induced autoantibodies cross-reacts with TAF9 protein and induces lupus-like autoimmunity in BALB/c mice. 3254 94
