The antiproliferative activity of the tetrapeptide Acetyl-N-SerAspLysPro, an inhibitor of haematopoietic stem cell proliferation, is not mediated by a thymosin beta 4-like effect on actin assembly.
Acetyl-N-SerAspLysPro (AcSDKP), known as a negative regulator of haematopoiesis, has been principally reported as an inhibitor of haematopoietic pluripotent stem cell proliferation. The tetrapeptide sequence is identical to the N-terminus of thymosin beta 4 (T beta 4), from which it has been suggested that it may be derived. Recently, evidence was shown that T beta 4 plays a role as a negative regulator of actin polymerization leading to the sequestration of its monomeric form. The structural similarity between the N-terminus of T beta 4 and AcSDKP has raised the possibility that AcSDKP may also participate in intracellular events leading to actin sequestration. The effect of T beta 4 on the proliferation of haematopoietic cells was compared to that of AcSDKP. The results revealed that T beta 4, like AcSDKP, exerts an inhibitory effect on the entry of murine primitive bone marrow cells into cell cycle in vitro. Qualitative electrophoretic analysis and quantitative polymerization assays were used to investigate the role of AcSDKP in actin polymerization. AcSDKP does not affect actin assembly at concentrations up to 50 microM, and does not compete with T beta 4 for binding to G-actin. These results suggest that AcSDKP is not involved in cell cycle regulation via an effect on the process of actin polymerization.
Cheviron
N
N
Intitut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Grillon
C
C
Carlier
M F
MF
Wdzieczak-Bakala
J
J
D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000737:chemistry*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008808:Mice, Inbred CBA; D009842:Oligopeptides / Q000494:pharmacology*; D013947:Thymosin / Q000494:pharmacology*; D000099201:Thymosin beta(4)
D000199:Actins; D006131:Growth Inhibitors; D009842:Oligopeptides; D013947:Thymosin; D000099201:Thymosin beta(4); C058504:goralatide