wt p53 dependent expression of a membrane-associated isoform of adenylate kinase

Licio Collavin, Dejan Lazarevič, René Utrera, Stefania Marzinotto, Martin Monte, Claudio Schneider

Research output: Contribution to journalArticle

Abstract

Six novel p53-inducible transcripts were recently cloned from Val5, a murine cell line stably expressing a temperature-sensitive p53 allele. One of the isolated clones represented a novel isoform of cytosolic adenylate kinase (AK1), a highly conserved monomeric enzyme involved in cellular homeostasis of adenine nucleotides. The corresponding protein, which we named AK1β, was specifically induced upon activation of wt p53 in Val5 cells. The AK1β protein differs from cytoplasmic AK1 by having 18 extra amino acids at the N-terminus. The extra residues in AK1β provide a consensus signal for N-terminal myristoylation; as expected, AK1β was shown to localize to the plasma membrane. The human AK1 gene contains several consensus p53 binding sites and we report that p53-dependent induction of the alternative AK1β transcript also occurs in human cells. By using antisense ablation experiments in Val5 fibroblasts wve show that AK1β plays a relevant role in the establishment of reversible cell-cycle arrest as induced by p53 in these cells. These findings suggest that within a p53-dependent genetic program, a specific isoform of adenylate kinase has a previously undescribed growth-regulatory function, which might not necessarily require its best characterized biochemical activity.

Original languageEnglish
Pages (from-to)5879-5888
Number of pages10
JournalOncogene
Volume18
Issue number43
DOIs
Publication statusPublished - Oct 21 1999

Fingerprint

Adenylate Kinase
Protein Isoforms
Membranes
Adenine Nucleotides
Cell Cycle Checkpoints
Proteins
Homeostasis
Clone Cells
Fibroblasts
Alleles
Binding Sites
Cell Membrane
Amino Acids
Cell Line
Temperature
Enzymes
Growth
Genes

Keywords

  • Adenylate kinase
  • p53 tumor suppressor
  • Val5 fibroblasts

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Collavin, L., Lazarevič, D., Utrera, R., Marzinotto, S., Monte, M., & Schneider, C. (1999). wt p53 dependent expression of a membrane-associated isoform of adenylate kinase. Oncogene, 18(43), 5879-5888. https://doi.org/10.1038/sj.onc.1202970

wt p53 dependent expression of a membrane-associated isoform of adenylate kinase. / Collavin, Licio; Lazarevič, Dejan; Utrera, René; Marzinotto, Stefania; Monte, Martin; Schneider, Claudio.

In: Oncogene, Vol. 18, No. 43, 21.10.1999, p. 5879-5888.

Research output: Contribution to journalArticle

Collavin, L, Lazarevič, D, Utrera, R, Marzinotto, S, Monte, M & Schneider, C 1999, 'wt p53 dependent expression of a membrane-associated isoform of adenylate kinase', Oncogene, vol. 18, no. 43, pp. 5879-5888. https://doi.org/10.1038/sj.onc.1202970
Collavin, Licio ; Lazarevič, Dejan ; Utrera, René ; Marzinotto, Stefania ; Monte, Martin ; Schneider, Claudio. / wt p53 dependent expression of a membrane-associated isoform of adenylate kinase. In: Oncogene. 1999 ; Vol. 18, No. 43. pp. 5879-5888.
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