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:6.3.5.5 (
CPS
)
1,262
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Rheb
small GTPases, which consist of Rheb1 and Rheb2 (also known as RhebL1) in mammalian cells, are unique members of the Ras superfamily and play central roles in regulating protein synthesis and cell growth by activating mTOR. To gain further insight into the function of
Rheb
, we carried out a search for
Rheb
-binding proteins and found that
Rheb
binds to CAD protein (
carbamoyl-phosphate synthetase
2, aspartate transcarbamoylase, and dihydroorotase), a multifunctional enzyme required for the de novo synthesis of pyrimidine nucleotides. CAD binding is more pronounced with Rheb2 than with Rheb1.
Rheb
binds CAD in a GTP- and effector domain-dependent manner. The region of CAD where
Rheb
binds is located at the C-terminal region of the
carbamoyl-phosphate synthetase
domain and not in the dihydroorotase and aspartate transcarbamoylase domains.
Rheb
stimulated
carbamoyl-phosphate synthetase
activity of CAD in vitro. In addition, an elevated level of intracellular UTP pyrimidine nucleotide was observed in Tsc2-deficient cells, which was attenuated by knocking down of
Rheb
. Immunostaining analysis showed that expression of
Rheb
leads to increased accumulation of CAD on lysosomes. Both a farnesyltransferase inhibitor that blocks membrane association of
Rheb
and knockdown of
Rheb
mislocalized CAD. These results establish CAD as a downstream effector of
Rheb
and suggest a possible role of
Rheb
in regulating de novo pyrimidine nucleotide synthesis.
...
PMID:Rheb protein binds CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase) protein in a GTP- and effector domain-dependent manner and influences its cellular localization and carbamoyl-phosphate synthetase (CPSase) activity. 2542 19
