A novel cyclin encoded by a bcl1-linked candidate oncogene

Area of Science:

• Molecular Biology
• Oncology
• Cell Cycle Regulation

Background:

• A candidate oncogene, PRAD1 (D11S287E), on chromosome 11q13 is rearranged with the parathyroid hormone locus in some benign parathyroid tumors.
• Cyclins are key regulators of cell cycle progression through complex formation and activation of p34cdc2 protein kinase.

Purpose of the Study:

• To characterize the PRAD1 gene and its encoded protein.
• To investigate the role of PRAD1 in cell cycle regulation and its potential involvement in tumor development.

Main Methods:

• Cloning and expression of human placental PRAD1 complementary DNA.
• Assessing PRAD1 mRNA levels across the cell cycle in HeLa cells.
• In vitro kinase assays using clam embryo lysates, PRAD1 protein, and p13suc1-bound beads to study p34cdc2 complex formation and activity.
• Measuring histone H1 phosphorylation as an indicator of p34cdc2 kinase activity.

Main Results:

• The cloned PRAD1 complementary DNA encodes a 295-amino acid protein with significant sequence similarity to cyclins.
• PRAD1 mRNA levels exhibit dramatic fluctuations during the cell cycle in HeLa cells.
• PRAD1 protein addition to cell lysates facilitated p34cdc2 kinase isolation and induced histone H1 phosphorylation, indicating PRAD1's ability to activate p34cdc2.
• PRAD1 protein forms a complex with and activates p34cdc2 kinase.

Conclusions:

• PRAD1 encodes a novel cyclin.
• Overexpression of this PRAD1 cyclin, potentially driven by 11q13 abnormalities, is implicated in the pathogenesis of various tumors.