The role of modulatory calcineurin-interacting proteins in calcineurin signaling.
Modulatory calcineurin-interacting proteins (MCIPs), also known as the Down syndrome critical region 1 (DSCR1) and DSCR1-like proteins, are a recently described family of small, structurally related proteins that are preferentially expressed in heart, skeletal muscle, and brain. MCIP proteins can bind to and inhibit calcineurin, a calcium/calmodulin-regulated serine/threonine protein phosphatase that is activated during cardiac hypertrophy and failure. Transcription of the mammalian MCIP1 gene is induced by calcineurin, suggesting that it functions as an endogenous feedback regulator of calcineurin signal transduction. Forced expression of human MCIP1 protein in the hearts of transgenic mice attenuates the hypertrophic response to a broad range of stimuli. This review summarizes work from a number of laboratories on the structure, regulation, and function of MCIP proteins.
Rothermel
Beverly A
BA
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA. rothermel@UTSouthwestern.edu
Vega
Rick B
RB
Williams
R Sanders
RS
D000818:Animals; D019703:Calcineurin / Q000235:genetics* / Q000502:physiology; D065095:Calcineurin Inhibitors; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D019703:Calcineurin