22954

TRIM32

BBS11|HT2A|LGMD2H|TATIP;tripartite motif containing 32;TRIM32;tripartite motif containing 32

72 kDa Tat-interacting protein|E3 ubiquitin-protein ligase TRIM32|TAT-interactive protein, 72-KD|tripartite motif-containing 32|tripartite motif-containing protein 32|zinc finger protein HT2A|zinc-finger protein HT2A

9q33.1

protein-coding

Asymmetric cell division (ACD) is a physiologic process during development and tissue homeostasis. ACD produces two unequal daughter cells: one has stem/progenitor cell activity and the other has potential for differentiation. Recent studies showed that misregulation of the balance between self-renewal and differentiation by ACD may lead to tumorigenesis in Drosophila neuroblasts. However, it is still largely unknown whether human cancer stem-like cells exhibit ACD or not. Here, using human neuroblastoma cells as an ACD model, we found that MYCN accumulates at spindle poles by GSK-3beta phosphorylation during mitosis. In parallel, the ACD-related ubiquitin ligase Trim32 was recruited to spindle poles by CDK1/cyclin B-mediated phosphorylation. Trim32 interacted with MYCN at spindle poles during mitosis, facilitating proteasomal degradation of MYCN at spindle poles and inducing ACD. Trim32 also suppressed sphere formation of neuroblastoma-initiating cells, suggesting that the mechanisms of ACD produce differentiated neuroblastoma cells that will eventually die. Thus, Trim32 is a positive regulator of ACD that acts against MYCN and should be considered as a tumor-suppressor candidate. Our findings offer novel insights into the mechanisms of ACD and clarify its contributions to human tumorigenesis.