The Transcription of Genes

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Arnica montana L. (Arnica) has been used for treating bruises and swelling in Western medicine on account of its ability to elaborate sesquiterpene lactones, such as hele-nalin and dihydrohelenalin, which are thought to inhibit the activation of transcription factor nuclear factor (NF)-kB, which is responsible for the transcription of genes involved in encoding mediators for the inflammatory process. 

Retinoic acid works through a family of retinoic acid receptors. Activated retinoic acid receptors act as transcription factors, just as activated steroid receptors do (chapter 20), and alter the transcription of genes affecting cell division and survival. This underlies both the teratogenic potential and the therapeutic utilities of these potent molecules. 

Regulatory proteins (transcription factors) are involved in controlling gene expression in all cells. These regulatory proteins bind to specific DNA sequences and thereby activate or inhibit the transcription of genes (Transcription control). The effects of transcription factors are usually reversible and are often controlled by ligands or by interconversion. 

The Gi-S transition (not shown) is particularly important for initiating the cell cycle, it is triggered by the CDK4-cyclin D complex, which by phosphorylating the protein pRb releases the transcription factor E2F previously bound to pRb. This activates the transcription of genes needed for DNA replication. 

The transcription of genes for metallothionein is imder positive regulation by the DNA-binding protein ACE, which binds an ACE-specific DNA element in the metal-... 

Cyclin E also performs its function in Gi/S phase. It demonstrates a periodic concentration change with a maximal value at the start of S phase. Afterwards, its concentration falls off sharply within S phase. The gene for cyclin E is also induced by transcription factor E2F which explains the increase in cyclin E at the Gi/S transition. Cyclin E binds and activates CDK2. The activated CDK2 complex is also involved in phosphorylation of the pRb protein. As a consequence, a signal is transmitted, with cooperation of cyclin D, in the direction of the transcription of genes that are essential for the continuation of the cell cycle. 

The drug indirectly alters the regulation of intracellular calcium levels via protein kinase C and can alter the transcription of gene- (downregulating) encoding enzymes (e.g., ATP/ADP translocase) and those involved in energy production and specific for cardiac tissue. 

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