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:P50502 (
Hip
)
7,003
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
fragile X mental retardation 1
(
FMR1
) protein binds mRNA and acts as a negative regulator of translation. Lack of
FMR1
causes the most common neurological disorder, fragile X syndrome, while its overexpression is associated with metastasis of breast cancer. Its activity has been well-studied in nervous tissue, but recent evidence as well as its role in cancer indicates that it also acts in other tissues. We have investigated the expression of
FMR1
in brain and other tissues of mouse and examined its regulation. We detected expression of
FMR1
in liver and heart tissues of mice as well as in brain tissue, supporting other contentions that it acts in non-nervous tissue. Expression of
FMR1
inversely correlated with expression of the C-terminus of
Hsc70-interacting protein
(CHIP) and, based on the known activity of CHIP in protein homeostasis, we suggest that CHIP regulates expression of
FMR1
. CHIP ubiquitinated
FMR1
for proteasomal degradation in a molecular chaperone-independent manner.
FMR1
expression was reduced following treatment with okadaic acid, a phosphatase inhibitor, but not in CHIP-depleted cells. Also, a non-phospho
FMR1
mutant was much less efficiently ubiquitinated by CHIP and had a longer half-life compared to either wild-type FMR or a phospho-mimic mutant. Taken together, our results demonstrate that CHIP regulates the levels of
FMR1
as an E3 ubiquitin ligase in phosphorylation-dependent manner, suggesting that CHIP regulates
FMR1
-mediated translational repression by regulating the levels of
FMR1
.
...
PMID:Regulation of fragile X mental retardation 1 protein by C-terminus of Hsc70-interacting protein depends on its phosphorylation status. 2526 20
