TRIM proteins in neuroblastoma

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Outcome for children with high-risk NB remains unsatisfactory. Accumulating evidence suggests that tripartite motif (TRIM) family proteins express diversely in various human cancers and act as regulators of oncoproteins or tumor suppressor proteins. This review summarizes the TRIM proteins involving in NB and the underlying molecular mechanisms. We expect these new insights will provide important implications for the treatment of NB by targeting TRIM proteins.

Keywords: E3 ubiquitin ligase; TRIM proteins; neuroblastoma; ubiquitination.

Figure 1. TRIM proteins domain structure and classification of TRIMs (C-I to C-XI)

TRIMs have an N-terminal RING finger (R), one or two B-boxes (B1 and B2), and coiled coil (CC) domain. C-terminal domains comprise various domains including: ARF, ADP-ribosylation factor family domain; BROMO, bromodomain; COS, cos-box; FIL, filamin-type Ig domain; FN3, fibronectin type III repeat; MATH, meprin and TRAF-homology domain; NHL, NCL1, HT2A and LIN41 domain; PHD, PHD domain; PRY, PRY domain; SPRY, SPRY domain; TM, transmembrane region. Dashed-outline domains are those which are differentially present among subfamily members.

Figure 2. Kaplan–Meier analysis of overall survival (left side) and event-free survival (right side) for the Kocak datasets based on TRIM36 expression with the log-rank test P value indicated (n = 649, with 173 samples lack survival data and being omitted from the analysis)