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:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
PEA3, ERM and ER81 belong to the PEA3 subfamily of Ets transcription factors and play important roles in a number of tissue-specific processes. Transcriptional activation by PEA3 subfamily factors requires their characteristic amino-terminal acidic transactivation domain (TAD). However, the cellular targets of this domain remain largely unknown. Using ERM as a prototype, we show that the minimal N-terminal TAD activates transcription by contacting the activator interacting domain (ACID)/Prostate tumor overexpressed protein 1 (PTOV) domain of the Mediator complex subunit
MED25
. We further show that depletion of
MED25
disrupts the association of ERM with the Mediator in vitro. Small interfering RNA-mediated knockdown of
MED25
as well as the overexpression of
MED25
-ACID and
MED25
-VWA domains efficiently inhibit the transcriptional activity of ERM. Moreover, mutations of amino acid residues that prevent binding of
MED25
to ERM strongly reduce transactivation by ERM. Finally we show that siRNA depletion of
MED25
diminishes PEA3-driven expression of
MMP-1
and Mediator recruitment. In conclusion, this study identifies the PEA3 group members as the first human transcriptional factors that interact with the
MED25
ACID/PTOV domain and establishes
MED25
as a crucial transducer of their transactivation potential.
...
PMID:The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members. 2353 47
