Steroid fingers

BLOCKS searches can be performed using the BLOCKS Web site at the Fred Hutchinson Cancer Research Center in Seattle. The Web site is straightforward, allowing both sequence-based and keyword-based searches to be performed. If a DNA sequence is used as the input, users can specify which genetic code to use and which strand to search. Regardless of whether the query is performed via a sequence or via keywords, a successful search will return the relevant block. An example is shown in Figme 11.3. In this entry (for a nuclear hormone receptor called a steroid finger). 

Figure 11.3. Structure of a typical BLOCKS entry. This is part of the entry for one block associated with steroid fingers. The structure of the entry is discussed in the text.

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

Steroids Cholesterol oxidation (haem) Zn fingers Haem oxidation... 

Horie, K., et al.. Estrogen-responsive Ring-finger protein controls breast cancer growth. J Steroid Biochem Mol Biol, 2003, 85(2-5), 101-4. 

Steroid receptors HRE Steroid response Zinc finger... 

Cortisol secreted in response to stress, is permissive for glucagon in hypoglycemia and acts through an intracellular receptor, which, like other steroid receptors, is a zinc-finger DNA binding protein,... 

Answer B. All intracellular receptors for steroid hormones are zinc-finger proteins. 

Answen Q Proteins with SH2 domains might bind to the insulin receptor substrate-1 (IRS-1) to transmit signals from the insulin receptor, a tyrosine kinase type of receptor. PI-3 kinase is an example of an SH2 domain protein. SH2 domains are not involved in DNA binding (choices A and D). Examples of protein domains that bind DNA include zinc fingers (steroid receptors), leudne zippers (CREB protein), and helix-turn-helbc proteins (homeodomain proteins),... 

Schwabe, J. W. R., and D. Rhodes, Beyond zinc fingers Steroid hormone receptors have a novel structural motif for DNA recognition. Trends Biochem. Sci. 16 291-296, 1991. 

Pinsker MO, Kinzel D, Lumenta CB. Epidural thoracic lipomatosis induced by long-term steroid treatment case illustration. Acta Neurochir (Wien) 1998 140(9) 991-2. Parker CT, Jarek MJ, Finger DR. Corticosteroid-associated epidural hpomatosis. J Clin Rheumatol 1999 5 141-2. 

Freedman, L. P Anatomy of the Steroid Receptor Zinc Finger Region. Endocr. Rev. 1992,13, 129-145. 

The C4 zinc finger is also found in a number of transcription factors, including steroid hormone receptor proteins. This motif forms a similar structure to that of C2H2 zinc finger but has four cysteines co-ordinated to the zinc ion instead of two cysteines and two histidines (see Fig. 4c). 

Zinc-fingers are common in DNA-binding proteins of eukaryotes but are not found in prokaryotes. Examples of zinc-finger proteins include the RNA polymerase III transcription factor TFIIIA, steroid receptors, and some gene products that control development. The zinc-finger consists of pairs of cysteine and/or histidine residues within an a-helix. These residues bind tightly to a Zn2+ ion, which allows the a-helical amino acids to interact with specific sequences. See Figure 12-18. 

Fig. 3. DNA-binding finger structure proposed for TFIIIA [21] and steroid receptors. The amino acid sequence of the glucocorticoid receptor (GR) fingers are shown. Conserved amino acids in the receptors for progesterone (PR) and oestrogen (ER) are indicated by an asterisk, whereas differences are shown.

These receptors are chiefly responsible for the physiological effects of steroid hormones such as cortisol as well as thyroid hormone and vitamin A. They are proteins that share a common basic structure consisting of a ligand binding domain and a DNA binding domain (comprised of zinc finger motifs). They operate as ligand-responsive transcription factors (see Chap. 17 for further discussion). 

The glucocorticoid receptor is a nuclear protein that has three functionally important domains a domain at the C terminus that binds steroid hormone (ligand), a DNA-binding domain composed of two zinc finger motifs and an N-terminal domain involved in the regulation of gene transcription (Fig. 6-20). 

An example of gene expression can be illustrated by consideration of the action of steroid hormones, and in the control of sterol biosynthesis. Steroid hormones enter the cell by diffusion through the plasma membrane and bind to their steroid hormone receptor. These receptors are part of a large related family that includes those for glucocorticoids, oestrogens, androgens, thyroid hormone, calcitriol and the retinoids. All steroid hormone receptors are zinc finger transcription factors. The receptor must ... 

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