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: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Accumulation of nucleotide building blocks prior to and during S phase facilitates DNA duplication. Herein, we find that the anaphase-promoting complex/cyclosome (
APC
/C) synchronizes
ribose-5-phosphate
levels and DNA synthesis during the cell cycle. In late G
1
and S phases, transketolase-like 1 (TKTL1) is overexpressed and forms stable TKTL1-transketolase heterodimers that accumulate
ribose-5-phosphate
. This accumulation occurs by asymmetric production of
ribose-5-phosphate
from the non-oxidative pentose phosphate pathway and prevention of
ribose-5-phosphate
removal by depleting transketolase homodimers. In the G
2
and M phases after DNA synthesis, expression of the
APC
/C adaptor CDH1 allows
APC
/C
CDH1
to degrade D-box-containing TKTL1, abrogating
ribose-5-phosphate
accumulation by TKTL1. TKTL1-overexpressing cancer cells exhibit elevated
ribose-5-phosphate
levels. The low CDH1 or high TKTL1-induced accumulation of
ribose-5-phosphate
facilitates nucleotide and DNA synthesis as well as cell cycle progression in a
ribose-5-phosphate
-saturable manner. Here we reveal that the cell cycle control machinery regulates DNA synthesis by mediating
ribose-5-phosphate
sufficiency.
...
PMID:APC/C
CDH1
synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression. 3117 80
