When the DREAM is gone: from basic science to future prospectives in pain management and beyond.
DREAM (downstream regulatory element antagonistic modulator) was identified as a novel calcium-binding protein with pleiotropic functions in vitro that are as varied as that of a transcription factor, a binding partner for presenilins, and a modulator of potassium channels. This review will discuss the findings that have implicated DREAM in its various roles. As a transcriptional repressor, DREAM may control the expression of the endogenous opioid gene prodynorphin amongst others, and itself is exquisitely regulated by second messenger molecules, protein kinases and other transcription factors. Recent genetic evidence has revealed a physiological role for DREAM in pain modulation. The interplay between DREAM and prodynorphin is discussed in light of our current understanding of this Janus-like opioid gene. The potential for the involvement of DREAM in other processes beyond pain modulation is considered at the end of this review.
Cheng
Hai-Ying M
HY
University Health Network/Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada. hymcheng@yahoo.ca
Penninger
Josef M
JM
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004745:Enkephalins / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008969:Molecular Sequence Data; D010146:Pain / Q000188:drug therapy*; D000699:Pain Insensitivity, Congenital / Q000235:genetics; D015221:Potassium Channels / Q000502:physiology; D053766:Presenilin-2; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D000700:Analgesics; C496756:Csen protein, mouse; D004745:Enkephalins; C496749:KCNIP3 protein, human; C496760:Kcnip3 protein, rat; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D015221:Potassium Channels; D053766:Presenilin-2; D011498:Protein Precursors; D012097:Repressor Proteins; C033660:preproenkephalin