+1 Proteins and aging

F W van Leeuwen, L Gerez, R Benne, E M Hol

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Molecular misreading is an expression used to describe errors in RNA that lead to the translation of mutated proteins. We have shown that dinucleotide deletions (delta GA, delta GU) are introduced in simple sequence repeats (e.g. GAGAG) of mRNA. If the resulting mutant transcripts escape RNA quality control systems, they are translated into +1 proteins. If functional domains are located downstream of the frameshift site, the result will be a protein with either a partial or complete loss of function. A clear example is ubiquitin(+1) (UBB(+1)), which has lost its capacity to ubiquitinate, i.e. tagging proteins destined for proteasomal degradation. This is an important step in regulating the degradation of misfolded proteins and transcription factors. In fact, UBB(+1) seems to block the proteasome. UBB(+1) and other proteins accumulate in the neuropathological hallmarks of Alzheimer's disease (AD), which suggests a causal relationship. We have hypothesized that quality control mechanisms for both transcripts and proteins work less efficiently during aging. In this manner +1 proteins may become manifest and contribute to age-related diseases.

Original languageEnglish
Pages (from-to)1502-5
Number of pages4
JournalThe International Journal of Biochemistry & Cell Biology.
Volume34
Issue number11
Publication statusPublished - Nov 2002

Keywords

  • Aging
  • Alzheimer Disease
  • Frameshift Mutation
  • Humans
  • RNA, Messenger
  • Ubiquitin
  • Journal Article
  • Review

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