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ADP-ribosylation of chromosomal proteins and mouse mammary tumor virus gene expression. Glucocorticoids rapidly
Abstract:
The relationship between endogenous ADP-ribosylation of chromosomal proteins and glucocorticoid-regulated mouse mammary tumor virus gene expression was investigated in cultured mouse mammary tumor cells. It was observed that glucocorticoids quickly decreased endogenous (ADP-ribose)n on the nonhistone high mobility group (HMG) 14 and 17 proteins. The half-time for this loss was 8 and 17 min, respectively, for the two proteins. (ADP-ribose)n on HMG 1 and 2 and on histone H1 was less susceptible to hydrolysis during glucocorticoid treatment. The rapid loss of (ADP-ribose)n from HMG 14 and 17 occurred in the same time frame as the induction of mouse mammary tumor virus RNA synthesis by glucocorticoids in these cells (Young, H. A., Shih, T. Y., Scolnick, E. M., and Parks, W. P. (1977) J. Virol. 21, 139-149). 3-Amino-benzamide, a specific inhibitor of (ADP-ribose)n synthetase, increased mouse mammary tumor virus RNA levels with an accompanying decrease in endogenous ADP-ribosylation of HMG 14 and 17. These results show that a decrease in endogenous ADP-ribosylation of HMG 14 and 17 is a consequence of glucocorticoid action and suggest that loss of (ADP-ribose)n from these proteins may be an important event in mouse mammary tumor virus gene expression.
Insights
Glucocorticoids rapidly decrease ADP-ribosylation on specific chromosomal proteins (HMG 14 and 17), which is linked to mouse mammary tumor virus gene activation. This suggests a key role for ADP-ribosylation in gene regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cancer Research
Background:
- Glucocorticoids are key regulators of gene expression.
- ADP-ribosylation is a post-translational modification involved in various cellular processes.
- Mouse mammary tumor virus (MMTV) is an oncogenic retrovirus whose expression is influenced by glucocorticoids.
Purpose of the Study:
- To investigate the relationship between endogenous ADP-ribosylation of chromosomal proteins and glucocorticoid-regulated MMTV gene expression.
- To determine the specific chromosomal proteins affected by glucocorticoid treatment and their role in MMTV gene expression.
Main Methods:
- Cultured mouse mammary tumor cells were treated with glucocorticoids.
- Endogenous ADP-ribosylation levels of various chromosomal proteins, including High Mobility Group (HMG) 14 and 17, were measured.
- The effect of 3-amino-benzamide, an ADP-ribosylation inhibitor, on MMTV RNA levels was assessed.
Main Results:
- Glucocorticoids rapidly decreased ADP-ribosylation on HMG 14 and 17 proteins (half-times of 8 and 17 minutes, respectively).
- ADP-ribosylation on HMG 1 and 2 and histone H1 was less affected by glucocorticoids.
- 3-Amino-benzamide increased MMTV RNA levels and decreased ADP-ribosylation of HMG 14 and 17.
Conclusions:
- A decrease in endogenous ADP-ribosylation of HMG 14 and 17 is a direct consequence of glucocorticoid action.
- The loss of ADP-ribosylation from HMG 14 and 17 proteins may be a critical event in the regulation of mouse mammary tumor virus gene expression.