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Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids.
Rong, Yao; Darnell, Alicia M; Sapp, Kiera M; Vander Heiden, Matthew G; Spencer, Sabrina L.
Afiliación
  • Rong Y; Department of Molecular, Cellular, and Developmental Biology and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
  • Darnell AM; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Sapp KM; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Vander Heiden MG; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02139, USA.
  • Spencer SL; Department of Biochemistry and BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA. Electronic address: sabrina.spencer@colorado.edu.
Cell Rep ; 42(12): 113539, 2023 12 26.
Article en En | MEDLINE | ID: mdl-38070134
Amino acids are required for cell growth and proliferation, but it remains unclear when and how amino acid availability impinges on the proliferation-quiescence decision. Here, we used time-lapse microscopy and single-cell tracking of cyclin-dependent kinase 2 (CDK2) activity to assess the response of individual cells to withdrawal of single amino acids and found strikingly different cell-cycle effects depending on the amino acid. For example, upon leucine withdrawal, MCF10A cells complete two cell cycles and then enter a CDK2-low quiescence, whereas lysine withdrawal causes immediate cell-cycle stalling. Methionine withdrawal triggers a restriction point phenotype similar to serum starvation or Mek inhibition: upon methionine withdrawal, cells complete their current cell cycle and enter a CDK2-low quiescence after mitosis. Modulation of restriction point regulators p21/p27 or cyclin D1 enables short-term rescue of proliferation under methionine and leucine withdrawal, and to a lesser extent lysine withdrawal, revealing a checkpoint connecting nutrient signaling to cell-cycle entry.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Quinasas CDC2-CDC28 Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Ciclo Celular / Quinasas CDC2-CDC28 Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos