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2015 ; 290
(47
): 28200-28213
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A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB
Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor
#MMPMID26442585
Wang Y
; Zheng Z
; Zhang J
; Wang Y
; Kong R
; Liu J
; Zhang Y
; Deng H
; Du X
; Ke Y
J Biol Chem
2015[Nov]; 290
(47
): 28200-28213
PMID26442585
show ga
Retinoblastoma protein (RB) plays critical roles in tumor suppression and is
degraded through the proteasomal pathway. However, E3 ubiquitin ligases
responsible for proteasome-mediated degradation of RB are largely unknown. Here
we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes
RB degradation. NRBE3 contains an LXCXE motif and bound RB in vitro. NRBE3
interacted with RB in cells when proteasome activity was inhibited. NRBE3
promoted RB ubiquitination and degradation via the ubiquitin-proteasome pathway.
Importantly, purified NRBE3 ubiquitinated recombinant RB in vitro, and a U-box
was identified as essential for its E3 activity. Surprisingly, NRBE3 was
transcriptionally activated by E2F1/DP1. Consequently, NRBE3 affected the cell
cycle by promoting G1/S transition. Moreover, NRBE3 was up-regulated in breast
cancer tissues. Taken together, we identified NRBE3 as a novel ubiquitin E3
ligase for RB that might play a role as a potential oncoprotein in human cancers.