Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/43552
Title: Regulation of p53 oligomerization by Ras superfamily protein RBEL1A
Authors: Lui, K
Saeed, SM
Huang, Y
Keywords: Oligomerization
P53 tumor suppressor
Ras superfamily GTPase
RBEL1A
Issue Date: 2015
Publisher: Impact Journals LLC
Source: Genes and cancer, 2015, v. 6, no. 7-8, p. 307-316 How to cite?
Journal: Genes and cancer 
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 radiationmediated 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. Implications: Elevated RBEL1A expression in human tumors could negatively regulate p53 by inhibiting its tetramerization.
URI: http://hdl.handle.net/10397/43552
ISSN: 1947-6019
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