ROS and p53 in regulation of UVB-induced HDM2 alternative splicing

Photochem Photobiol. 2015 Jan-Feb;91(1):221-4. doi: 10.1111/php.12306. Epub 2014 Jul 26.

Abstract

Alternative splicing plays an important role in proteasome diversity and gene expression regulation in eukaryotic cells. Hdm2, the human homolog of mdm2 (murine double minute oncogene 2), is known to be an oncogene as its role in suppression of p53. Hdm2 alternative splicing, occurs in both tumor and normal tissues, is believed to be a response of cells for cellular stress, and thus modulate p53 activity. Therefore, understanding the regulation of hdm2 splicing is critical in elucidating the mechanisms of tumor development and progression. In this study, we determined the effect of ultraviolet B light (UVB) on alternative splicing of hdm2. Our data indicated that UVB (50 mJ cm(-2)) alone is not a good inducer of alternative splicing of hdm2. The less effectiveness could be due to the induction of ROS and p53 by UVB because removing ROS by L-NAC (10 mm) in p53 null cells could lead to alternative splicing of hdm2 upon UVB irradiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Cell Line, Tumor
  • Humans
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Reactive Oxygen Species / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays*

Substances

  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2