The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from ...The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.展开更多
The past five years have witnessed the discovery of the endoplasmic reticulum calcium(Ca2+) sensor STIM1 and the plasma membrane Ca2+channel Orai1 as the bona fide molecular components of the store-operated Ca2+ entry...The past five years have witnessed the discovery of the endoplasmic reticulum calcium(Ca2+) sensor STIM1 and the plasma membrane Ca2+channel Orai1 as the bona fide molecular components of the store-operated Ca2+ entry(SOCE) and the Ca2+ release-activated Ca2+current(I CRAC) .It has been known for two decades that SOCE and ICRAC are required for lymphocyte activation as evidenced by severe immunodeficient phenotypes in patients lacking ICRAC.In recent years however,studies have uncovered expression of STIM1 and Orai1 proteins in various tissues and described additional roles for these proteins in physiological functions and pathophysiological conditions.Here,we will summarize novel findings pertaining to the role of STIM1 and Orai1 in the vascular system and discuss their potential use as targets in the therapy of vascular disease.展开更多
文摘The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.
基金supported by the National Institutes of Health(Grant No. 5R01HL097111)to Mohamed Trebak
文摘The past five years have witnessed the discovery of the endoplasmic reticulum calcium(Ca2+) sensor STIM1 and the plasma membrane Ca2+channel Orai1 as the bona fide molecular components of the store-operated Ca2+ entry(SOCE) and the Ca2+ release-activated Ca2+current(I CRAC) .It has been known for two decades that SOCE and ICRAC are required for lymphocyte activation as evidenced by severe immunodeficient phenotypes in patients lacking ICRAC.In recent years however,studies have uncovered expression of STIM1 and Orai1 proteins in various tissues and described additional roles for these proteins in physiological functions and pathophysiological conditions.Here,we will summarize novel findings pertaining to the role of STIM1 and Orai1 in the vascular system and discuss their potential use as targets in the therapy of vascular disease.
