Inhibition of cyclin D-cdk activity in cell cycle arrest of Swiss 3T3 cells by CeReS-18, a novel cell regulatory sialoglycopeptide.

Abstract

CeReS-18 is a unique negative regulator of cell proliferation with a wide array of target cells. To elucidate the mechanism by which CeReS-18 mediates cell growth inhibition, the possibility that CeReS-18 alters the function of G1 cyclins and their respective cyclin-dependent kinases (cdks) has been examined in mouse fibroblasts (Swiss 3T3) synchronized by CeReS-18. We show here that cyclin D-associated cdk activity is significantly inhibited in the CeReS-18-treated cells. Corresponding to the inhibited cdk function, we demonstrate a low expression of cyclin D in mid G1 determined by Western blot analysis, and cyclin D was greatly reduced in the immunocomplex recovered with antibody to cdk4 and cdk6. Previously, we have shown that the retinoblastoma susceptibility gene product (pRb), a key substrate of cyclin D-cdk complex, was maintained in the hypophosphorylated state in the CeReS-18-inhibited cells. We conclude here that cyclin D/cdk4,6/pRb is the major pathway by which CeReS-18 mediates cell cycle arrest.

• Authors: K Zhao, H K Fattaey, T M Quinton, T C Johnson
• Journal: Experimental cell research (Exp Cell Res) Vol. 244 Issue 1 Pg. 295-301 (Oct 10 1998) ISSN: 0014-4827 [Print] United States
• PMID: 9770372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• CeReS-18 protein, Bos taurus
• Cyclin D
• Cyclins
• Proto-Oncogene Proteins
• Sialoglycoproteins
• Protein Serine-Threonine Kinases
• CDC2-CDC28 Kinases
• Cdk2 protein, mouse
• Cdk4 protein, mouse
• Cdk6 protein, mouse
• Cyclin-Dependent Kinase 2
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6
• Cyclin-Dependent Kinases

Topics

• 3T3 Cells
• Animals
• CDC2-CDC28 Kinases
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cyclin D
• Cyclin-Dependent Kinase 2
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6
• Cyclin-Dependent Kinases (antagonists & inhibitors, biosynthesis)
• Cyclins (antagonists & inhibitors, biosynthesis)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• G1 Phase (drug effects)
• Mice
• Protein Serine-Threonine Kinases (biosynthesis)
• Proto-Oncogene Proteins
• Sialoglycoproteins (pharmacology)
• Time Factors