DEREGULATION OF CYCLIN E AND CDK INHIBITOR IN LYMPHOID CELL

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 07671183
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: TOKYO MEDICAL AND DENTAL UNIVERSITY
• Principal Investigator: TAKASE Kozo TOKYO MEDICAL AND DENTAL UNIVERSITY,M.D., Ph.D., 医学部, 助手 (90211333)
• Project Period (FY): 1995 – 1996
• Keywords: CDK inhibitor / cyclin E / NAD / DMSO

Research Abstract

We investigated the relationship between the cell cycle status and the regulation of cyclin E expression on DMSO-arrested Raji cells. In arrested Raji Cells, abundant cyclin E and a detectable amount of cdk2 are observed in contrast to normal resting T cells where a small amount of cdk2 and an undetectable amount of cyclin E present. The enzyme activity of cyclin E or cdk2 in Raji cells is not demonstrated until just before the cell cycle recovery from DMSO-induced arrest, in regardless to the abundance of these components of the enzyme. As for the stimulation induced proliferation of normal T cells, the enzyme activity of cyclin E or cdk2 arises in a time course manner parallel to the appearance of cyclin E protein. Along this process, any known inhibitor against cdk is not detected as an obvious band in Western blotting. These indicate that the regulatory mechanisms of cyclin E/cdk2 activity in normal T cells and cell lines are quite different, and that the dysregulation of cell cycle progression in cell line is not supposed to be attributed by a deficiency of cdk inhibitor. In addition, we demonstrated an accumulation and a rapid consumption of NAD^+ across the cell cycle recovery from DMSO-arrest in Raji cells. We assume an activation of poly (ADP-ribose) polymerase plays an important role in this phenomenon where the amount of AMP is observed to increase in a reciprocal manner to the decrease in NAD^+.