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:P36959 (
guanosine monophosphate reductase
)
36
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Melanoma progression is associated with increased invasion and, often, decreased levels of
microphthalmia-associated transcription factor
(
MITF
). Accordingly, downregulation of
MITF
induces invasion in melanoma cells; however, little is known about the underlying mechanisms. Here, we report for the first time that depletion of
MITF
results in elevation of intracellular GTP levels and increased amounts of active (GTP-bound) RAC1, RHO-A and RHO-C. Concomitantly,
MITF
-depleted cells display larger number of invadopodia and increased invasion. We further demonstrate that the gene for
guanosine monophosphate reductase
(
GMPR
) is a direct
MITF
target, and that the partial repression of
GMPR
accounts mostly for the above phenotypes in
MITF
-depleted cells. Reciprocally, transactivation of
GMPR
is required for
MITF
-dependent suppression of melanoma cell invasion, tumorigenicity and lung colonization. Moreover, loss of
GMPR
accompanies downregulation of
MITF
in vemurafenib-resistant BRAF
V600E
-melanoma cells and underlies the increased invasion in these cells. Our data uncover novel mechanisms linking
MITF
-dependent inhibition of invasion to suppression of guanylate metabolism.
...
PMID:Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools. 2718 Dec 9
