Selective induction of cell cycle regulatory genes cdk1 (p34cdc2), cyclins a/b, and the tumor suppressor gene RB in transformed cells by okadaic acid
✍ Scribed by Jinsong You; R. Curtis Bird
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 962 KB
- Volume
- 164
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Genes encoding cdkl (~34'~''), cyclin A, cyclin B, and the tumor suppressor gene Rb are fundamental regulators of cell cycle progression which associate as a complex with the transcription factor E2F. Expression of many of these proteins has previously been shown to be repressed by okadaic acid, a specific inhibitor of protein phosphatases 112A (PPl/PPZA), resulting in growth arrest in nontransformed but immortilized cells. We have investigated levels of mRNA encoding cdkl ( ~3 4 ' ~~' ) , cyclin A, cyclin B, Rb, GAPDH, c-mytr, and histone H4 genes for sensitivity to okadaic acid in HeLa cells to determine if transformation altered their regulation. Serum starvation slowed growth and diminished mRNA levels for all genes tested except c-myc and GAPDH. When starved cells were subsequently exposed to 19 n M okadaic acid or refed 10% serum, mRNA levels ot cyclin A, cyclin B, cdkl, and Rb dramatically increased while mRNA levels for c-myc and