Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca2+ Homeostasis

Sánchez-Collado, José; López, José J.; Jardín, Isaac; Salido, Ginés M.; Rosado, Juan A.

doi:10.1007/112_2020_55

Cited by 13 publications

(16 citation statements)

References 286 publications

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“…AC isoforms are located throughout the organism, displaying specific locations and presenting cell and tissue-specific expression patterns [ 129 ]. ACs are classically activated by G-proteins downstream G-protein coupled receptors, but additionally, AC1 and AC8 are activated by Ca 2+ [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. cAMP is a basic second messenger that has a major function in cellular physiology.…”

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

“…Its compartmentalization is regulated by scaffold proteins that form complexes with PKA to anchor it close to target molecules. Several studies demonstrated that SOCE or SOCE components can trigger AC5, AC6, and AC8 activation [ 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. AC8 is regulated by Ca 2+ and exhibits a low affinity for this ion.…”

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

“…Hypothetically, the absence of the cAMP signaling complex close to Orai1β-assembled channels might have consequences in Ca 2+ signaling. It is known that cAMP modulate Ca 2+ homeostasis (extensively discussed in [ 136 ]). In summary, the high [cAMP] c microenvironment generated around activated Orai1α subunits regulates not only I crac but also other Ca 2+ -handling mechanisms.…”

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

“…In cancer cells, the cAMP/PKA pathway promotes proliferation, migration, and invasive properties, as well as other aspects of their physiology [ 151 ]. Moreover, the Orai1 channel is a well-known regulator of proliferation and migration in breast cancer cells [ 136 , 152 ]. Therefore, the SOCE-dependent cAMP signaling might have increased importance in breast cancer biology since both Orai1 and AC8 have been found to be highly expressed in these cells [ 93 , 153 , 154 , 155 , 156 ].…”

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

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Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β

Jardín

Berna‐Erro

Nieto‐Felipe

et al. 2022

IJMS

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Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.

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Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

Section: Regulation Of Orai1α By Ac8 In Breast Cancer Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β

Jardín

Berna‐Erro

Nieto‐Felipe

et al. 2022

IJMS

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“…The adenylate cyclase (ADCY) gene family, which encodes AC proteins, plays important regulatory roles in a spectrum of biological processes like cell proliferation, apoptosis, migration, invasion, angiogenesis, abnormal metabolism, and immune escape (9)(10)(11). AC compounds are already in clinical use for certain diseases such as neuropathic pain, neurodegenerative diseases, congestive heart failure, asthma, and male contraception (12).…”

Section: Introductionmentioning

confidence: 99%

Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy

et al. 2022

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The adenylate cyclase (ADCY) superfamily is a group of glycoproteins regulating intracellular signaling. ADCYs act as key regulators in the cyclic adenosine monophosphate (cAMP) signaling pathway and are related to cell sensitivity to chemotherapy and ionizing radiation. Many members of the superfamily are detectable in most chemoresistance cases despite the complexity and unknownness of the specific mechanism underlying the role of ADCYs in the proliferation and invasion of cancer cells. The overactivation of ADCY, as well as its upstream and downstream regulators, is implicated as a major potential target of novel anticancer therapies and markers of exceptional responders to chemotherapy. The present review focuses on the oncogenic functions of the ADCY family and emphasizes the possibility of the mediating roles of deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) in ADCY as a prognostic therapeutic target in modulating resistance to chemotherapy and immunotherapy. It assesses the mediating roles of ADCY and its counterparts as stress regulators in reprogramming cancer cell metabolism and the tumor microenvironment. Additionally, the well-evaluated inhibitors of ADCY-related signaling, which are under clinical investigation, are highlighted. A better understanding of ADCY-induced signaling and deleterious nsSNPs (p.E1003K and p.R1116C) in ADCY6 provides new opportunities for developing novel therapeutic strategies in personalized oncology and new approaches to enhance chemoimmunotherapy efficacy in treating various cancers.

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Role of Orai‐family channels in the activation and regulation of transcriptional activity

Nieto‐Felipe

Macias‐Diaz

Sánchez-Collado

et al. 2023

Journal Cellular Physiology

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Store operated Ca2+ entry (SOCE) is a cornerstone for the maintenance of intracellular Ca2+ homeostasis and the regulation of a variety of cellular functions. SOCE is mediated by STIM and Orai proteins following the activation of inositol 1,4,5‐trisphosphate receptors. Then, a reduction of the endoplasmic reticulum intraluminal Ca2+ concentration is sensed by STIM proteins, which undergo a conformational change and activate plasma membrane Ca2+ channels comprised by Orai proteins. STIM1/Orai‐mediated Ca2+ signals are finely regulated and modulate the activity of different transcription factors, including certain isoforms of the nuclear factor of activated T‐cells, the cAMP‐response element binding protein, the nuclear factor κ‐light chain‐enhancer of activated B cells, c‐fos, and c‐myc. These transcription factors associate SOCE with a plethora of signaling events and cellular functions. Here we provide an overview of the current knowledge about the role of Orai channels in the regulation of transcription factors through Ca2+‐dependent signaling pathways.

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Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca2+ Homeostasis

Cited by 13 publications

References 286 publications

Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β

Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β

Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy

Role of Orai‐family channels in the activation and regulation of transcriptional activity

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