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:C0027819 (
neuroblastoma
)
27,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
LAPTM5
(lysosomal-associated protein multispanning transmembrane 5) is a membrane protein on the intracellular vesicles. We have previously demonstrated that the accumulation of
LAPTM5
-positive vesicles was closely associated with the programmed cell death occurring during the spontaneous regression of neuroblastomas. Although the accumulation of
LAPTM5
protein might occur at the post-translational level, the molecular mechanism has been unclear. Here, we found that the level of
LAPTM5
protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of
LAPTM5
via its WW domains and promotes ubiquitination through a HECT-type ligase domain. Overexpression of ITCH led to the degradation of
LAPTM5
protein, and conversely, knockdown of ITCH by siRNA resulted in the stabilization of
LAPTM5
protein. In addition, the inhibition of ITCH enhanced the cell death occurred by accumulation of
LAPTM5
in
neuroblastoma
cells. These findings suggest that
LAPTM5
is a novel substrate in terms of degradation by the ubiquitin ligase ITCH, and this system might act as a negative regulator in the spontaneous regression of neuroblastomas by preventing
LAPTM5
-mediated cell death.
...
PMID:HECT-type ubiquitin ligase ITCH targets lysosomal-associated protein multispanning transmembrane 5 (LAPTM5) and prevents LAPTM5-mediated cell death. 2200 53
