Metabolic Activation of CaMKII by Coenzyme A

McCoy, Francis; Darbandi, Rashid; Lee, Hoi Chang; Bharatham, Kavitha; Moldoveanu, Tudor; Grace, Christy R.; Dodd, Keela; Lin, Wenwei; Chen, Si Ing; Tangallapally, Rajendra; Kurokawa, Manabu; Lee, Richard; Shelat, Anang A.; Chen, Taosheng; Green, Douglas R.; Harris, Robert A.; Lin, Sue Hwa; Fissore, Rafael A.; Colbran, Roger J.; Nutt, Leta K.

doi:10.1016/j.molcel.2013.10.027

Cited by 5 publications

(6 citation statements)

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“…PKC inhibitors can induce apoptosis in Xenopus laevis oocytes, which is in agreement with our findings that U73122 inhibits PKC and increases apoptosis in porcine oocytes. The activation of CAMKII has been previously found to inhibit apoptosis in Xenopus laevis oocyte and murine oocytes, which was in line with our finding that m‐3M3FBS inhibits CAMKIIα and decreases apoptosis. The knockdown of Caln in the oocytes of Xenopus further induced apoptosis, where Caln contributes to the rapid recovery of ER Ca 2+ homeostasis .…”

Section: Discussionsupporting

confidence: 91%

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

Chen

Cheng

Yang

et al. 2020

J of Cellular Biochemistry

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Oocyte apoptosis can be used as an indicator of oocyte quality and development competency. Phospholipase C (PLC) is a critical enzyme that participates in phosphoinositide metabolic regulation and performs many functions, including the regulation of reproduction. In this study, we aimed to explore whether PLC participates in the regulation of apoptosis in porcine oocytes and investigated its possible mechanism. In porcine oocytes, 0.5 μM U73122 (the PLC inhibitor) was considered to be the best concentration to facilitate maturation, and 0.5 μM m-3M3FBS (the PLC activator) was regarded as the most appropriate concentration to inhibit maturation. The percentage of cleavage and blastocysts treated with 0.5 μM U73122 was lower than that of the control group. Furthermore, the percentage of cleavage and blastocysts treated with 0.5 μM m-3M3FBS was higher than that of the control group. The relative PLC messenger RNA (mRNA) expression tested by a quantitative real-time polymerase chain reaction was found to be inhibited by 0.5 μM U73122 or activated by 0.5 μM m-3M3FBS. The relative mRNA abundance of BAK, BAX, CASP3, CASP8, and TP53 and protein abundance of Bak, cleaved caspase-3, caspase-8, and P53 was activated by U73122 or inhibited by m-3M3FBS, while the relative mRNA and protein level of BCL6 showed the opposite trend. The intracellular Ca 2+ concentration increased and the expression of PLCB1 protein also increased in porcine oocytes when they were cultured with 0.5 μM m-3M3FBS for 44 hours. The abundance of proteins PKCβ and CAMKIIα and the expression of several downstream genes (CDC42, NFATc1, NFATc2, NFκB, and NLK) were activated by m-3M3FBS or inhibited by U73122. Our findings indicate that PLC inhibits apoptosis and maturation in porcine oocytes. The intracellular Ca 2+ concentration, two Ca 2+ -sensitive proteins, and several downstream genes were positively regulated by PLC. K E Y W O R D Sapoptosis, Ca 2+ -sensitive proteins, intracellular Ca 2+ concentration, oocytes, phospholipase C, porcine

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Section: Discussionsupporting

confidence: 91%

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

Chen

Cheng

Yang

et al. 2020

J of Cellular Biochemistry

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“…In line, fatty acid oxidation-generated acetyl-CoA supported calcium/calmodulin-dependent kinase II (CaMKII) activity in prostate cancer cells that resulted in reduced anoikis and cell migration 152 . Thereby, the presumed mechanism may depend on acetyl-CoA-derived CoA, generated locally by a yet to be identified acetyl-CoA hydrolysing reaction, and consecutive bind-ing to the calmodulin (CaM)-binding domain of CaMKII to promote CaM binding and activation of CaMKII at basal calcium concentrations 153 . Moreover, a recent study demonstrated in mice bearing patient-derived melanomas that cancer cells metastasizing through the lymphatic sys-tem conveyed reduced levels of ROS-induced ferroptosis compared with cells metastasizing through the blood vas-cular system 154 .…”

Section: In Summary Fatty Acid Metabolism Can Increase Tumour Cell Migration and Invasion By Altering Cellular Signalling Cues And Regulamentioning

confidence: 99%

The metabolism of cancer cells during metastasis

2021

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Metastasis formation is the major cause of death in most patients with cancer. Despite extensive research, targeting metastatic seeding and colonization is still an unresolved challenge. Only recently, attention has been drawn to the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade. Moreover, many metastases display different metabolic traits compared with the tumours from which they originate, enabling survival and growth in the new environment. Consequently, the stage-dependent metabolic traits may provide therapeutic windows for preventing or reducing metastasis, and targeting the new metabolic traits arising in established metastases may allow their eradication.The metastatic establishment of cancers at distant organs is largely uncurable and primarily contributes to the deaths of cancer patients. Nonetheless, metastasis for-mation itself is a rare event in tumours because cancer cells need to overcome multiple environmental hur-dles before they can successfully manifest themselves in other organs 1,2 . As a first step, cancer cells need to become motile, invasive and intravasate the tumour vasculature to enter the bloodstream, either directly or via the lymphatic system. Although numerous cancer cells can find their way into the circulation, the majority will succumb during their journey, with only few able to extravasate, expand and successfully colonize other organs 3 . Clinical observations and multiple experi-mental studies have led to several propositions that can explain the acquired metastatic traits of cancer cells (as described and summarized elsewhere 2-7

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“…In this way, W214 might serve as a docking site for CaMKII-specific interactions. Additionally, a previous study suggested that the pantothenate segment of Coenzyme A packs against W214 of CaMKII to mediate this interaction [41].…”

Section: Resultsmentioning

confidence: 99%

“…Densin-180 does not have a helical motif, which may explain why the W214A mutant does not have a drastic effect. A role for W214 was also proposed as a result of MD simulations between CaMKII and Coenzyme A [37].…”

Section: Discussionmentioning

confidence: 97%

CaMKII binds both substrates and activators at the active site

Ozden

Sloutsky

Santos

et al. 2020

Preprint

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Ca2+/calmodulin dependent protein kinase II (CaMKII) is a signaling protein that is required for successful long-term memory formation. Ca2+/CaM activates CaMKII by binding to its regulatory segment, thereby making the substrate binding pocket available. One exceptional feature of this kinase is that two binding partners have been shown persistently activate CaMKII after the Ca2+ stimulus dissipates. The molecular details of this phenomenon are unclear. Despite having a large variety of interaction partners, the specificity of CaMKII has not been structurally well-characterized. To this end, we solved X-ray crystal structures of the CaMKII kinase domain bound to four different binding partners: a peptide substrate, a substrate/activator, a substrate/binding partner, and an inhibitor (AMPA-type glutamate receptor, NMDA-type glutamate receptor, Tiam1, and Densin-180). We show that all four binding partners use similar interactions to bind across the substrate binding pocket of the CaMKII active site. We generated a sequence alignment based on our structural observations, which revealed conserved interactions across these binding partners. The structures presented here shed much-needed light on the interaction between CaMKII and its binding partners. These observations will be crucial in guiding further biological experiments.

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Metabolic Activation of CaMKII by Coenzyme A

Cited by 5 publications

References 0 publications

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro

The metabolism of cancer cells during metastasis

CaMKII binds both substrates and activators at the active site

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