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: EC:1.6.5.3 (
complex I
)
8,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This is due primarily to a reduction in the transcriptional activity of
TFIIIC
, a transcription factor which binds in a sequence specific manner to the internal promoter of pol III genes. Using gel retardation assays, we have shown previously that inhibition of pol III transcription by poliovirus is correlated with disappearance of a transcriptionally active form of
TFIIIC
(complex I) concomitant with the appearance of a faster mobility, transcriptionally inactive form of
TFIIIC
(complex III). We show here that a poliovirus with a point mutation in the proteinase 3C (3Cpro) region failed to produce complex III and is limited in its ability to inhibit pol III transcription compared with the wild-type virus. Incubation of purified 3Cpro, expressed in Escherichia coli, with transcriptionally active
TFIIIC
(complex I) in vitro resulted in generation of the transcriptionally inactive complex III form of
TFIIIC
. In an in vitro transcription assay, treatment of the
complex I
form of
TFIIIC
with 3Cpro almost completely inhibited pol III transcription. Finally expression of the 3Cpro gene in transfected HeLa cells resulted in significant inhibition of pol III-mediated transcription. The results presented here suggest that proteolysis of the transcriptionally active form of
TFIIIC
by poliovirus 3Cpro is a mechanism by which poliovirus inhibits host cell RNA pol III transcription.
...
PMID:Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus. 191 71
In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This inhibition is due primarily to the reduction in transcriptional activity of the pol III transcription factor
TFIIIC
in poliovirus-infected cells. However, the specific binding of
TFIIIC
to the VAI gene B-box sequence, as assayed by DNase I footprinting, is not altered by poliovirus infection. We have used gel retardation analysis to analyze
TFIIIC
-DNA complexes formed in nuclear extracts prepared from mock- and poliovirus-infected cells. In mock-infected cell extracts, two closely migrating
TFIIIC
-containing complexes, complexes I and II, were detected in the gel retardation assay. The slower migrating complex,
complex I
, was absent in poliovirus-infected cell extracts, and an increase occurred in the intensity of the faster-migrating complex (complex II). Also, in poliovirus-infected cell extracts, a new, rapidly migrating complex, complex III, was formed. Complex III may have been the result of limited proteolysis of
complex I
or II. These changes in
TFIIIC
-containing complexes in poliovirus-infected cell extracts correlated kinetically with the decrease in
TFIIIC
transcriptional activity. Complexes I, II, and III were chromatographically separated; only
complex I
was transcriptionally active and specifically restored pol III transcription when added to poliovirus-infected cell extracts. Acid phosphatase treatment partially converted
complex I
to complex II but did not affect the binding of complex II or III. Dephosphorylation and limited proteolysis of
TFIIIC
are discussed as possible mechanisms for the inhibition of pol III-mediated transcription by poliovirus.
...
PMID:A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells. 220 7
