Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase.

ABSTRACT: Inactivation of the retinoblastoma gene (RB1) product, pRB, is common in many human cancers. Targeting downstream effectors of pRB that are central to tumorigenesis is a promising strategy to block the growth of tumors harboring loss-of-function RB1 mutations. One such effector is retinoblastoma-binding protein 2 (RBP2, also called JARID1A or KDM5A), which encodes an H3K4 demethylase. Binding of pRB to RBP2 has been linked to the ability of pRB to promote senescence and differentiation. Importantly, genetic ablation of RBP2 is sufficient to phenocopy pRB's ability to induce these cellular changes in cell culture experiments. Moreover, germline Rbp2 deletion significantly impedes tumorigenesis in Rb1^+/- mice. The value of RBP2 as a therapeutic target i

SUBMITTER: McBrayer SK 

PROVIDER: S-EPMC5910822 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature