Furin is the major proprotein convertase required for KISS1-to-Kisspeptin processing.
KISS1 is a broadly functional secreted proprotein that is then processed into small peptides, termed kisspeptins (KP). Since sequence analysis showed cleavage at KR or RR dibasic sites of the nascent protein, it was hypothesized that enzyme(s) belonging to the proprotein convertase family of proteases process KISS1 to generate KP. To this end, cell lines over-expressing KISS1 were treated with the proprotein convertase inhibitors, Dec-RVKR-CMK and α1-PDX, and KISS1 processing was completely inhibited. To identify the specific enzyme(s) responsible for KISS1 processing, mRNA expression was systematically analyzed for six proprotein convertases found in secretory pathways. Consistent expression of the three proteases - furin, PCSK5 and PCSK7 - were potentially implicated in KISS1 processing. However, shRNA-mediated knockdown of furin - but not PCSK5 or PCSK7 - blocked KISS1 processing. Thus, furin appears to be the essential enzyme for the generation of kisspeptins.
Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Sitaram
S
Harihar
Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; Department of Molecular Physiology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Keke M
KM
Pounds
Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; Department of Molecular Physiology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Tomoo
T
Iwakuma
Clinical Research Institute of Montreal, affiliated to Université de Montréal, Montréal, Québec, Canada.
Nabil G
NG
Seidah
Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; Department of Molecular Physiology, The University of Kansas Medical Center, Kansas City, Kansas, United States of America ; Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Danny R
DR
Welch
D045744:Cell Line, Tumor; D045683:Furin / Q000378:metabolism*; D006801:Humans; D059648:Kisspeptins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D011499:Protein Processing, Post-Translational
C106628:KISS1 protein, human; D059648:Kisspeptins; D045683:Furin