An important element of calcium signaling pathways involves calmodulin activation of calcineurin (phosphatase PP2B), leading to dephosphorylation of transcription factors such as NFAT and MEF2. A wide variety of proteins other than calmodulin have also been implicated in regulating calcineurin activity. Regulators of Calcineurin (RCANs) include RCAN1, RCAN2, and RCAN3. RCAN1 has previously been referred to as Down's syndrome candidate region-1 (Dscr1), MCIP, calcipressin, and Adapt78. This RCAN is expressed as several different variants with RCAN1L (38 kDa) and RCAN1S (31 kDa) being most prevalent. RCAN1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Increased expression of RCAN1 leads to significant suppression of tumor growth in mice as result of deficits in calcineurin-induced tumor angiogenesis. RCAN1 can recruit TAB1, TAK1, and calcineurin into a macromolecular signaling complex, and TAK1 can phosphorylate Ser-94 and Ser-136 in RCAN1S. This phosphorylation converts RCAN1 from an inhibitor to a facilitator of calcineurin-NFAT signaling.
Baek, K.H. et al. (2009) Nature. 459(7250):1126.
Liu, Q. et al. (2009) Nat Cell Biol. 11:154.
*For more information, see UniProt Accession P53805
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*All molecular weights (MW) are confirmed by comparison to Bio-Rad Rainbow Markers and to western blot mobilities of known proteins with similar MW.
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