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:1.10.3.1 (
tyrosinase
)
9,065
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxysterols play a significant role in cholesterol homeostasis. 25-Hydroxycholesterol (25HC) in particular has been demonstrated to regulate cholesterol homeostasis via oxysterol-binding protein and oxysterol-related proteins, the sterol regulatory element binding protein, and the rate-limiting enzyme of cholesterol biosynthesis, hydroxymethylglutaryl coenzyme A reductase. We have examined the effect of 25HC on pigmentation of cultured murine melanocytes and demonstrated a decrease in pigmentation with an IC(50) of 0.34 microM and a significant diminution in levels of melanogenic protein
tyrosinase
. Pulse-chase studies of 25HC-treated cells demonstrated enhanced degradation of
tyrosinase
, the rate-limiting enzyme of melanin synthesis, following endoplasmic reticulum (ER) and Golgi maturation. Protein levels of GS28, a member of an ER/cis-Golgi
SNARE
protein complex, were also diminished in 25HC-treated melanocytes, however levels of the ER chaperone calnexin and the cis-Golgi matrix protein GM130 were unaffected. Effects of 25HC on
tyrosinase
were completely reversed by 4 alpha-allylcholestan-3 alpha-ol, a sterol identified by its ability to reverse effects of 25HC on cholesterol homeostasis. Finally, the addition of 25HC to lipid deficient serum inhibited correct processing of
tyrosinase
. We conclude that 25HC acts in the Golgi compartment to regulate pigmentation by a mechanism shared with cholesterol homeostasis.
...
PMID:25-hydroxycholesterol acts in the Golgi compartment to induce degradation of tyrosinase. 1525 Sep 42
Historically, studies on the maturation and intracellular transport of melanosomes in melanocytes have greatly contributed to elucidating the general mechanisms of intracellular transport in many different types of mammalian cells. During melanosome maturation, melanosome cargoes including melanogenic enzymes (e.g.
tyrosinase
) are transported from endosomes to immature melanosomes by membrane trafficking, which must require a membrane fusion process likely regulated by SNAREs [
s
oluble
N
SF (
N
-ethylmaleimide-sensitive factor)
a
ttachment protein
re
ceptors]. In the present study, we review the literature concerning the expression and function of SNAREs (e.g. v-SNARE vesicle-associated membrane protein 7 and t-SNAREs syntaxin-3/13 and synaptosomal-associated protein-23) in melanocytes, especially in regard to the fusion process in which melanosome cargoes are finally delivered to immature melanosomes. We also describe the recent discovery of the
SNARE
recycling system on mature melanosomes in melanocytes. Such
SNARE
dynamics, especially the
SNARE
recycling system, on melanosomes will be useful in understanding as yet unidentified
SNARE
dynamics on other organelles.
...
PMID:SNARE dynamics during melanosome maturation. 3002 69