Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor
Carr SM., Munro S., Zalmas L-P., Fedorov O., Johansson C., Krojer T., Sagum CA., Bedford MT., Oppermann U., La Thangue NB.
Significance The retinoblastoma protein (pRb) is a key regulator of cell cycle progression and the DNA damage response. Its importance in these processes is highlighted by the fact that it is mutated or functionally inactivated in almost all human tumors. Its activity is finely regulated by a number of post-translational modifications, including phosphorylation and methylation, which act to recruit “reader” proteins that mediate signaling events. Here, to our knowledge for the first time, we describe the methyl-dependent interaction between pRb and the tudor domain containing tumor protein p53 binding protein 1 (53BP1) and describe how this interaction integrates pRb cell cycle control with the DNA damage response. Our results therefore widen the repertoire of cellular targets for 53BP1 and suggest a new role in regulating pRb tumor suppressor activity.