title: Regulation of p53 oligomerization by Ras superfamily protein RBEL1A.
abstract: Our previous studies showed that RBEL1A overexpressed in multiple human malignancies and its depletion by RNAi caused severe growth inhibition in tumor cells. We also showed that RBEL1A directly interacted with p53 and such interactions occurred at the oligomeric domain of p53. However, the effect of such interactions on p53 oligomerization and function remained to be investigated. Here, we report that the interaction of RBEL1A and p53 suppressed p53 oligomer formation in unstressed cells and in cells exposed to DNA damage. Furthermore, purified RBEL1A blocked the oligomerization of recombinant p53 corresponding to residues 315-360 in vitro. RBEL1A also significantly reduced the oligomerization of the exogenously expressed C-terminal region (residues 301-393) of p53 in cells. Overexpression of RBEL1A (as seen in human tumors), also suppressed oligomerization by endogenous p53. Our results also showed that GTPase domain of RBEL1A at residues 1-235 was sufficient to block p53 oligomerization. Furthermore, silencing of endogenous RBEL1A significantly enhanced the formation of p53 oligomeric complex following ultraviolet radiation-mediated DNA damage and RBEL1A knockdown also enhanced expression of p53 target genes. Taken together, our studies provide important new molecular insights into the regulation of p53 and the oncogenic role of RBEL1A in the context to human malignancy.
  
  
  CONCLUSIONS
  Elevated RBEL1A expression in human tumors could negatively regulate p53 by inhibiting its tetramerization.
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, USA ; Division of Science and Technology, The Hong Kong Polytechnic University, Hong Kong Community College, Hung Hom, Kowloon, Hong Kong.
authors.forename: Ki
authors.initials: K
authors.lastname: Lui
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, USA.
authors.forename: M Saeed
authors.initials: MS
authors.lastname: Sheikh
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
keywords: RBEL1A; Ras superfamily GTPase; oligomerization; p53 tumor suppressor