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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2001

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Opposing functions of Ki- and Ha-Ras genes in the regulation of redox signals

Anno di pubblicazione: 2001

Autori: Mariarosaria Santillo, Paolo Mondola, Rosalba Serý, Tiziana Annella, Silvana Cassano, Ilaria Ciullo, Mario F. Tecce, Giuseppe Iacomino, Simona Damiano, Giovanni Cuda, Roberto PaternÚ, Valeria Martignetti, Evelina Mele, Antonio Feliciello, and Enrico V. Av

Affiliazioni autori: ISA-CNR

Autori CNR:

  • GIUSEPPE IACOMINO

Abstract: Ras p21 signaling is involved in multiple aspects of growth, differentiation, and stress response [1-2]. There is evidence pointing to superoxides as relays of Ras signaling messages. Chemicals with antioxidant activity suppress Ras-induced DNA synthesis. The inhibition of Ras significantly reduces the production of superoxides by the NADPH-oxidase complex [3]. Kirsten and Harvey are nonallelic Ras cellular genes that share a high degree of structural and functional homology. The sequences of Ki- and Ha-Ras proteins are almost identical. They diverge only in the 20-amino acid hypervariable domain at the COOH termini. To date, their functions remain indistinguishable [4]. We show that Ki- and Ha-Ras genes differently regulate the redox state of the cell. Ha-Ras-expressing cells produce high levels of reactive oxygen species (ROS) by inducing the NADPH-oxidase system. Ki-Ras, on the other hand, stimulates the scavenging of ROS by activating posttranscriptionally the mitochondrial antioxidant enzyme, Mn-superoxide dismutase (Mn-SOD), via an ERK1/2-dependent pathway. Glutamic acid substitution of the four lysine residues in the polybasic stretch at the COOH terminus of Ki-Ras completely abolishes the activation of Mn-SOD, although it does not inhibit ERK1/2-induced transcription. In contrast, an alanine substitution of the cysteine of the CAAX box has very little effect on Mn-SOD activity but eliminates ERK1/2- dependent transcription

Lingua abstract: inglese

Pagine da: 614

Pagine a: 619

Rivista:

Current biology Current Biology,
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 0960-9822

Numero volume: 11 (8

Parole chiave:

  • ras
  • redox
  • signaling

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