Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

Pasquini, Miriam; Grosjean, Nicolas; Hixson, Kim; Nicora, Carrie; Yee, Estella F.; Lipton, Mary; Blaby, Ian K.; Haley, John D.; Blaby-Haas, Crysten E.

doi:10.1016/j.celrep.2022.110834

Cited by 30 publications

(21 citation statements)

References 80 publications

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“…Remarkably, metallothioneins have critical roles in intracellular zinc homeostasis and buffering reactions due to their zinc binding and transport properties, as well as being a source of signaling zinc ions under redox signaling conditions [ 111 , 113 ]. In addition to the available zinc pools and metallothioneins, a number of studies in recent years have suggested that chaperone-mediated zinc ion transfer now becomes the third known mechanism for allocating zinc ions [ 114 , 115 , 116 ].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

Liu

Kong

et al. 2023

Nutrients

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Breast cancer has become the most common cancer worldwide. Despite the major advances made in the past few decades in the treatment of breast cancer using a combination of chemotherapy, endocrine therapy, and immunotherapy, the genesis, treatment, recurrence, and metastasis of this disease continue to pose significant difficulties. New treatment approaches are therefore urgently required. Zinc is an important trace element that is involved in regulating various enzymatic, metabolic, and cellular processes in the human body. Several studies have shown that abnormal zinc homeostasis can lead to the onset and progression of various diseases, including breast cancer. This review highlights the role played by zinc transporters in pathogenesis, apoptosis, signal transduction, and potential clinical applications in breast cancer. Additionally, the translation of the clinical applications of zinc and associated molecules in breast cancer, as well as the recent developments in the zinc-related drug targets for breast cancer treatment, is discussed. These developments offer novel insights into understanding the concepts and approaches that could be used for the diagnosis and management of breast cancer.

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Section: Discussionmentioning

confidence: 99%

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

Liu

Kong

et al. 2023

Nutrients

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“…Our findings suggest that it would be fruitful to explore whether or not other GTP-dependent metallochaperones enable the transfer of their cognate metals against unfavorable thermodynamic gradients. A client for the GE3 GTPase Zng1 has recently been identified as Zn II -requiring methionine aminopeptidase I. , Deletion of ZNG1 in Saccharomyces cerevisiae impairs Map1 activity which in turn inhibits growth under Zn II -deficient conditions . Similarly, zebrafish and mouse mutants in Zng1 show increased sensitivity to dietary Zn II starvation .…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, zebrafish and mouse mutants in Zng1 show increased sensitivity to dietary Zn II starvation . It has been suggested that Map1 may in effect be unable to compete with exchangeable labile Zn II buffer sites during Zn II limitation and the assistance of Zng1 prioritizes the metalation of Map1 under these conditions . Bacterial cells also prioritize metalation of critical Zn II clients under Zn II limitation by sparing Zn II demand from ribosomal subunits, − modeled to occur when the degree of buffer saturation equates to a 100-fold decrease in available [Zn II ] (Figure b from Osman and co-workers).…”

Section: Discussionmentioning

confidence: 99%

Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B₁₂

Young

Deery

Foster

et al. 2023

JACS Au

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The acquisition of Co II by the corrin component of vitamin B 12 follows one of two distinct pathways, referred to as early or late Co II insertion. The late insertion pathway exploits a Co II metallochaperone (CobW) from the COG0523 family of G3E GTPases, while the early insertion pathway does not. This provides an opportunity to contrast the thermodynamics of metalation in a metallochaperonerequiring and a metallochaperone-independent pathway. In the metallochaperoneindependent route, sirohydrochlorin (SHC) associates with the CbiK chelatase to form Co II -SHC. Co II -buffered enzymatic assays indicate that SHC binding enhances the thermodynamic gradient for Co II transfer from the cytosol to CbiK. In the metallochaperone-dependent pathway, hydrogenobyrinic acid a,c-diamide (HBAD) associates with the CobNST chelatase to form Co II -HBAD. Here, Co II -buffered enzymatic assays indicate that Co II transfer from the cytosol to HBAD-CobNST must somehow traverse a highly unfavorable thermodynamic gradient for Co II binding. Notably, there is a favorable gradient for Co II transfer from the cytosol to the Mg II GTP-CobW metallochaperone, but further transfer of Co II from the GTP-bound metallochaperone to the HBAD-CobNST chelatase complex is thermodynamically unfavorable. However, after nucleotide hydrolysis, Co II transfer from the chaperone to the chelatase complex is calculated to become favorable. These data reveal that the CobW metallochaperone can overcome an unfavorable thermodynamic gradient for Co II transfer from the cytosol to the chelatase by coupling this process to GTP hydrolysis.

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“…The other possibility is that the activity of certain chaperones that help coordinate zinc in KAT7 may be reduced under zinc-deficient conditions. Recent reports have demonstrated that proper zinc transport mediated by a zinc chaperone regulates the activity of the zinc-dependent enzymes 48,49 . Moreover, in vitro zinc repletion of KAT7 WT immunoprecipitated from the cells treated with TPEN did not fully restore the KAT7 HAT activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

Zinc controls histone acetyltransferase KAT7 activity to maintain cellular zinc homeostasis

Fujisawa,

Takenaka,

Maekawa

et al. 2023

Preprint

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Zinc is an indispensable micronutrient for optimal physiological function; therefore, zinc deficiency has been implicated in the pathogenesis of various human diseases. To address these deleterious conditions, our bodies have regulatory mechanisms that respond to zinc deficiency stress at the cellular level. However, the related molecular mechanisms, especially at the gene expression level, remain poorly understood. Here, we show that during zinc deficiency, the histone acetyltransferase KAT7 loses its enzymatic activity, leading to the attenuated acetylation of histone H3 at Lys14 (H3K14ac). Physiologically, this decrease in H3K14ac leads to the transcriptional upregulation of ZIP10, a plasma membrane-localized zinc transporter, thereby importing zinc from extracellular sources to maintain cellular zinc homeostasis. Our data demonstrate that cells respond to zinc deficiency stress by converting it into an epigenetic signal to drive cellular responses.

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Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

Cited by 30 publications

References 80 publications

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B₁₂

Zinc controls histone acetyltransferase KAT7 activity to maintain cellular zinc homeostasis

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Zng1 is a GTP-dependent zinc transferase needed for activation of methionine aminopeptidase

Cited by 30 publications

References 80 publications

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

A Systematic Study on Zinc-Related Metabolism in Breast Cancer

Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B12

Zinc controls histone acetyltransferase KAT7 activity to maintain cellular zinc homeostasis

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Product

Resources

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Two Distinct Thermodynamic Gradients for Cellular Metalation of Vitamin B₁₂