MDM2 but not MDM4 promotes retinoblastoma cell proliferation through p53-independent regulation of MYCN translation.

ABSTRACT: Retinoblastomas can arise from cone photoreceptor precursors in response to the loss of pRB function. Cone precursor-specific circuitry cooperates with pRB loss to initiate this process and subsequently contributes to the malignancy. Intrinsic high-level MDM2 expression is a key component of the cone precursor circuitry and is thought to inactivate p53-mediated tumor surveillance, which could otherwise be induced in response to pRB loss. However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression. Here we report that high-level MDM2 but not MDM4 has a consistent critical role in retinoblastoma cell proliferation in

SUBMITTER: Qi DL 

PROVIDER: S-EPMC5374018 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature