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:C0033774 (
pruritus
)
14,546
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nedd4-interacting protein 2 (
NDFIP2
) has three transmembrane domains and interacts with multiple Nedd4 family ubiquitin ligases through polyprolinetyrosine (PY) motifs located in its N-terminal cytoplasmic domain. It has been postulated that
NDFIP2
acts as an adaptor for the ubiquitylation of substrates with Nedd4 ubiquitin ligase. However, whether
NDFIP2
promotes or inhibits the ubiquitylation of Nedd4 substrates is still under debate. We show here that although
NDFIP2
is detected in the Golgi/trans-Golgi network (TGN) area, it is rapidly delivered to and degraded in lysosomes with its half-life ca. 1.5 h. Intriguingly, knockdown (KD) of
NDFIP2
with small interfering RNA (siRNA) impaired both the formation and function of gap junctions. Indeed, KD of
NDFIP2
destabilized the gap junction protein connexin43 that contains PY motif. In support of this, overexpression of
NDFIP2
stabilized connexin43 and enhanced the formation of gap junctions. Furthermore, the PY motifs of
NDFIP2
, which are required for its interaction with Nedd4, Atrophin-1 interacting protein (AIP) 4 (AIP4)/
Itch
, and AIP2/WWP2, were necessary for the targeting of
NDFIP2
to lysosomes and/or the stability of connexin43 and gap junctions. Collectively these findings suggest that
NDFIP2
may inhibit the Nedd4-dependent ubiquitylation of membrane proteins containing PY motifs, such as connexin43, in a competitive manner.
...
PMID:Nedd4-interacting protein 2, a short half-life membrane protein degraded in lysosomes, negatively controls down-regulation of connexin43. 2052 58
