Substrate specificity and inducibility of TACE (tumour necrosis factor alpha-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity.
Tumour necrosis factor alpha (TNF alpha)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor alpha, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.
Black
Roy A
RA
Amgen Inc., 51 University Street, Seattle, WA 98101, USA. blackra@amgen.com
Doedens
John R
JR
Mahimkar
Rajeev
R
Johnson
Richard
R
Guo
Lin
L
Wallace
Alison
A
Virca
Duke
D
Eisenman
June
J
Slack
Jennifer
J
Castner
Beverly
B
Sunnarborg
Susan W
SW
Lee
David C
DC
Cowling
Rebecca
R
Jin
Guixian
G
Charrier
Keith
K
Peschon
Jacques J
JJ
Paxton
Ray
R
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000409:Alanine / Q000378:metabolism*; D004790:Enzyme Induction; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014633:Valine / Q000378:metabolism*
D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; D014633:Valine; D000409:Alanine