Antiproliferative activity of CCN3: involvement of the C-terminal module and post-translational regulation.
Previous work had suggested that recombinant CCN3 was partially inhibiting cell proliferation. Here we show that native CCN3 protein secreted into the conditioned medium of glioma transfected cells indeed induces a reduction in cell proliferation. Large amounts of CCN3 are shown to accumulate both cytoplasmically and extracellularly as cells reach high density, therefore highlighting new aspects on how cell growth may be regulated by CCN proteins. Evidence is presented establishing that the amount of CCN3 secreted into cell culture medium is regulated by post-translational proteolysis. As a consequence, the production of CCN3 varies throughout the cell cycle and CCN3 accumulates at the G2/M transition of the cycle. We also show that CCN3-induced inhibition of cell growth can be partially reversed by specific antibodies raised against a C-terminal peptide of CCN3. The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition.
Bleau
A M
AM
Université Paris7-D. Diderot, UFR de Biochimie, Laboratoire d'Oncologie Virale et Moléculaire, 2 place Jussieu, 75005 Paris, France.
Planque
N
N
Lazar
N
N
Zambelli
D
D
Ori
A
A
Quan
T
T
Fisher
G
G
Scotlandi
K
K
Perbal
B
B
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor; D003470:Culture Media / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055514:Nephroblastoma Overexpressed Protein; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D003470:Culture Media; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor