Histone acetyltransferase MOF orchestrates outcomes at the crossroad of oncogenesis, DNA damage response, proliferation, and stem cell development

Mayank Singh, Albino Bacolla, Shilpi Chaudhary, Clayton R. Hunt, Shruti Pandita, Ravi Chauhan, Ashna Gupta, John A. Tainer, Tej K. Pandita

Research output: Contribution to journalReview article

Abstract

The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/ deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyltransferase (HAT) family of proteins performs histone acetylation. In humans, MOF (hMOF), a member of the MYST family of HATs, acetylates histone H4 at lysine 16 (H4K16ac). MOF-mediated acetylation plays a critical role in the DNA damage response (DDR) and embryonic stem cell development. Functionally, MOF is found in two distinct complexes: NSL (nonspecific lethal) in humans and MSL (male-specific lethal) in flies. The NSL complex is also able to acetylate additional histone H4 sites. Dysregulation of MOF activity occurs in multiple cancers, including ovarian cancer, medulloblastoma, breast cancer, colorectal cancer, and lung cancer. Bioinformatics analysis of KAT8, the gene encoding hMOF, indicated that it is highly overexpressed in kidney tumors as part of a concerted gene coexpression program that can support high levels of chromosome segregation and cell proliferation. The linkage between MOF and tumor proliferation suggests that there are additional functions of MOF that remain to be discovered.

Original languageEnglish (US)
Article numbere00232-20
JournalMolecular and Cellular Biology
Volume40
Issue number18
DOIs
StatePublished - Sep 1 2020

Keywords

  • Cancer
  • DDR
  • Histone acetyltransferase
  • MOF
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Histone acetyltransferase MOF orchestrates outcomes at the crossroad of oncogenesis, DNA damage response, proliferation, and stem cell development'. Together they form a unique fingerprint.

Cite this