Transsulfuration Activity Can Support Cell Growth upon Extracellular Cysteine Limitation
| Autor: | Justin R. Cross, Mirela Berisa, Craig B. Thompson, Jiajun Zhu, Weige Qin, Simon Schwörer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male S-Adenosylmethionine Physiology Mice Nude Transsulfuration Transsulfuration pathway Mice SCID Methylation Article 03 medical and health sciences chemistry.chemical_compound Gene Knockout Techniques Mice 0302 clinical medicine Methionine Mice Inbred NOD Neoplasms Extracellular Serine Animals Humans Cysteine Protamines Molecular Biology Cell Proliferation chemistry.chemical_classification Cell growth Cell Biology Glutathione Hep G2 Cells S-Adenosylhomocysteine Cell biology Tumor Burden 030104 developmental biology Enzyme chemistry A549 Cells MCF-7 Cells Heterografts Female Extracellular Space 030217 neurology & neurosurgery |
| Zdroj: | Cell Metab |
| ISSN: | 1932-7420 |
| Popis: | Summary Cysteine acts both as a building unit for protein translation and as the limiting substrate for glutathione synthesis to support the cellular antioxidant system. In addition to transporter-mediated uptake, cellular cysteine can also be synthesized from methionine through the transsulfuration pathway. Here, we investigate the regulation of transsulfuration and its role in sustaining cell proliferation upon extracellular cysteine limitation, a condition reported to occur in human tumors as they grow in size. We observed constitutive expression of transsulfuration enzymes in a subset of cancer cell lines, while in other cells, these enzymes are induced following cysteine deprivation. We show that both constitutive and inducible transsulfuration activities contribute to the cellular cysteine pool and redox homeostasis. The rate of transsulfuration is determined by the cellular capacity to conduct methylation reactions that convert S-adenosylmethionine to S-adenosylhomocysteine. Finally, our results demonstrate that transsulfuration-mediated cysteine synthesis is critical in promoting tumor growth in vivo. |
| Databáze: | OpenAIRE |
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