Centrosomal pericentrin is a direct cleavage target of membrane type-1 matrix metalloproteinase in humans but not in mice: potential implications for tumorigenesis
Authors: Alex Y Strongin
Alexei V Chekanov
Stephen J Doxsey
Vladislav S Golubkov
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MT1-MMP; pericentrin; cleavage; centrosomes; endocytosis
Affiliations: Cancer Research Center, The Burnham Institute for Medical Research, La Jolla, California 92037, USA.

Abstract:  Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits distinctive and important pericellular cleavage functions. Recently, we determined that MT1-MMP was trafficked to the centrosomes in the course of endocytosis. Our data suggested that the functionally important, integral, centrosomal protein, pericentrin-2, was a cleavage target of MT1-MMP in human and in canine cells and that the sequence of the cleavage sites were ALRRLLG1156 downward arrow L1157FG and ALRRLLS2068 downward arrow L2069FG, respectively. The presence of Asp-948 at the P1 position inactivated the corresponding site (ALRRLLD948-L949FGD) in murine pericentrin. To confirm that MT1-MMP itself cleaves pericentrin directly, rather than indirectly, we analyzed the cleavage of the peptides that span the MT1-MMP cleavage site. In addition, we analyzed glioma U251 cells, which co-expressed MT1-MMP with the wild type murine pericentrin and the D948G mutant. We determined that the D948G mutant that exhibited the cleavage sequence of human pericentrin was sensitive to MT1-MMP, whereas unmodified murine pericentrin was resistant to proteolysis. Taken together, our results confirm that MT1-MMP cleaves pericentrin-2 in humans but not in mice and that mouse models of cancer probably cannot be used to critically examine MT1-MMP functionality. 

Retracted: No

PubPeer comments:
 Figure 4A. * Some mice representing different treatment groups or timepoints appear to look remarkably similar. * The mice marked with red and blue boxes also look similar (could be different photos of the same mouse). Similarities between other mice are also noted. ![file]  The present work received grants from the Nature Science Foundation of Guangdong (S2012010009088) and the National Nature Science Foundation of China (81272806). , 
 Figure 5A. * Orange boxes: The PBS and the hMSCs panels appear to show an overlap * Aqua boxes: The hMSCs and the hMSCs-ephrin A1-PE38KDEL panels appear to show an overlap ![file] , 
 Retracted [31 August 2021] . ------------------------------ At the request of the authors, the Editor and Publisher of *Drug Design, Development and Therapy* wish to retract the published article. Concerns were raised regarding duplicated mouse images and cell staining images in Figures 4A and 5A, respectively. The authors were unable to locate the original data for their study and thus were unable to verify the validity of the data. To ensure the integrity of the publication record the authors requested to retract the paper and the editor has agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,