Modulation of a novel thermolysin-like metallo-endopeptidase activity during retinoic acid-induced differentiation of human neuroectodermal tumor cell lines.
Neuroectodermal tumours express hormones which are post-translationally processed and inactivated by the action of specific proteases and peptidases. The data reported here show the presence of a novel thermolysin-like metallo-endopeptidase activity in several human cell lines. The soluble fractions of neuroblastoma, melanoma and a glioblastoma tumour cell lines are able, with different degrees, to cleave the Ser12-Phe13 bond of a DVDERDVRGFAS decreases FLNH2 substrate. The inhibition pattern suggests a metallo-endopeptidase thermolysin-like character, with the involvement of thiol group(s), clearly distinct from neutral endopeptidase (NEP; EC 3.4.24.11). This metallo-endopeptidase activity is down regulated during retinoic acid(RA)-induced neuronal differentiation in the RA-sensitive SK-N-BE(2) cells but not in the RA-resistant BE(2)-M17 cells, suggesting that the down regulation is related to neuronal differentiation and not a direct effect of RA on the enzymatic activity.
Laboratoire de Biochimie des Signaux de Régulation Moléculaire et Cellulaire Université P.&M. Curie, Unité 554 CNRS, Paris, France.
K M
KM
Carvalho
V
V
De Laurenzi
G
G
Melino
P
P
Cohen
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D005910:Glioma; D006801:Humans; D007700:Kinetics; D008545:Melanoma; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009373:Neoplasms, Germ Cell and Embryonal; D015260:Neprilysin / Q000378:metabolism*; D009447:Neuroblastoma; D009842:Oligopeptides / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000201:enzymology; D013379:Substrate Specificity; D013820:Thermolysin / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D009842:Oligopeptides; D011994:Recombinant Proteins; D014212:Tretinoin; D008666:Metalloendopeptidases; D015260:Neprilysin; D013820:Thermolysin