ArticleMolecular and cellular biology2009
Domain architecture of the regulators of calcineurin (RCANs) and identification of a divergent RCAN in yeast.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- Familial Alzheimer's disease mutations in amyloid precursor protein impair calcineurin signaling to NMDA receptors.The Journal of biological chemistry · 2025Article
- Calcineurin associates with centrosomes and regulates cilia length maintenance.Journal of cell science · 2023Article
- DSCR1 deficiency ameliorates the Aβ pathology of Alzheimer's disease by enhancing microglial activity.Life science alliance · 2023Article
- Interaction of calcium responsive proteins and transcriptional factors with the PHO regulon in yeasts and fungi.Frontiers in cell and developmental biology · 2023Review
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Substrates of the MAPK Slt2: Shaping Yeast Cell Integrity.Journal of fungi (Basel, Switzerland) · 2022Review
- CRZ1 transcription factor is involved in cell survival, stress tolerance, and virulence in fungi.Journal of biosciences · 2022Review
- The feedback loop between calcineurin, calmodulin-dependent protein kinase II, and nuclear factor of activated T-cells regulates the number of GABAergic neurons during planarian head regeneration.Frontiers in molecular neuroscience · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Partial Inhibition of Calcineurin Activity by Rcn2 as a Potential Remedy for Vps13 Deficiency.International journal of molecular sciences · 2021Article
- Regulator of Calcineurin (RCAN): Beyond Down Syndrome Critical Region.Molecules and cells · 2020Review
- Identifying New Substrates and Functions for an Old Enzyme: Calcineurin.Cold Spring Harbor perspectives in biology · 2020Review
- A novel peptide exerts potent immunosuppression by blocking the two-site interaction of NFAT with calcineurin.The Journal of biological chemistry · 2020Article
- Ser/Thr protein phosphatases in fungi: structure, regulation and function.Microbial cell (Graz, Austria) · 2019Review
- Auxin-Inducible Depletion of the Essentialome Suggests Inhibition of TORC1 by Auxins and Inhibition of Vrg4 by SDZ 90-215, a Natural Antifungal Cyclopeptide.G3 (Bethesda, Md.) · 2019Article
- Milk biosynthesis requires the Golgi cation exchanger TMEM165.The Journal of biological chemistry · 2019Article
- The protein kinase Cmk2 negatively regulates the calcium/calcineurin signalling pathway and expression of calcium pump genes PMR1 and PMC1 in budding yeast.Cell communication and signaling : CCS · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Regulators of calcineurin (RCANs) in fungi and mammals have been shown to stimulate and inhibit calcineurin signaling in vivo through direct interactions with the catalytic subunit of the phosphatase. The dual effects of RCANs on calcineurin were examined by performing structure-function analyses on yeast Rcn1 and human RCAN1 (a.k.a. DSCR1, MCIP1, and calcipressin 1) proteins expressed at a variety of different levels in yeast. At high levels of expression, the inhibitory effects required a degenerate PxIxIT-like motif and a novel LxxP motif, which may be related to calcineurin-binding motifs in human NFAT proteins. The conserved glycogen synthase kinase 3 (GSK-3) phosphorylation site was not required for inhibition, suggesting that RCANs can simply compete with other substrates for docking onto calcineurin. In addition to these docking motifs, two other highly conserved motifs plus the GSK-3 phosphorylation site in RCANs, along with the E3 ubiquitin ligase SCF(Cdc4), were required for stimulation of calcineurin signaling in yeast. These findings suggest that RCANs may function primarily as chaperones for calcineurin biosynthesis or recycling, requiring binding, phosphorylation, ubiquitylation, and proteasomal degradation for their stimulatory effect. Finally, another highly divergent yeast RCAN, termed Rcn2 (YOR220w), was identified through a functional genetic screen. Rcn2 lacks all stimulatory motifs, though its expression was still strongly induced by calcineurin signaling through Crz1 and it competed with other endogenous substrates when overexpressed, similar to canonical RCANs. These findings suggest a primary role for canonical RCANs in facilitating calcineurin signaling, but canonical RCANs may secondarily inhibit calcineurin signaling by interfering with substrate interactions and enzymatic activity.
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