Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases

Mol Biol Rep. 2021 May;48(5):4747-4756. doi: 10.1007/s11033-021-06421-x. Epub 2021 May 27.

Abstract

AlkBH1 is a member of the AlkB superfamily which are kinds of Fe (II) and α-ketoglutarate (α-KG)-dependent dioxygenases. At present, only demethyltransferases FTO and AlkBH5 have relatively clear substrate studies among these members, the types and mechanisms of substrates catalysis of other members are not clear, especially the demethyltransferase AlkBH1. AlkBH1, as a demethylase, has important functions of reversing DNA methylation and repairing DNA damage. And it has become a promising target for the treatment of many cancers, the regulation of neurological and genetic related diseases. Many scholars have made important discoveries in the diversity of AlkBH1 substrates, but there is no comprehensive summary, which affects the design inhibitor target of AlkBH1. Herein, We are absorbed in the latest progress in the study of AlkBH1 substrate diversity and its relationship with human diseases. Besides, we also discuss future research directions and suggest other studies to reveal the specific catalytic effect of AlkBH1 on cancer substrates.

Keywords: AlkBH1; Demethyltransferase; Substrate diversity; Tumor progression.

Publication types

  • Review

MeSH terms

  • AlkB Homolog 1, Histone H2a Dioxygenase / genetics*
  • AlkB Homolog 5, RNA Demethylase / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • DNA Damage / genetics
  • DNA Methylation / genetics
  • DNA Repair / genetics
  • Humans
  • Ketoglutaric Acids / metabolism
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology
  • Substrate Specificity / genetics

Substances

  • Ketoglutaric Acids
  • ALKBH5 protein, human
  • AlkB Homolog 5, RNA Demethylase
  • ALKBH1 protein, human
  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human