Fig. 1

Retinoblastoma protein (pRb) structural domains and protein interactions. A Structured domains in pRb are colored, including the N-terminal domain (pRbN), the pocket domain A and B, and the pRb C-terminus core region (pRbC^core). In contrast, several intrinsically regions contain two large loops in pRbN (pRbNL) and the pocket domain (pRbPL), an interdomain linker (pRbIDL) and part of the N-terminal region of the pRbC (pRbC^N). N and C indicate the N- and C-terminals of the protein. Numbers indicate the amino acid positions. B Model of the unphosphorylated form of pRb and its interaction with E2F and LXCXE motif containing proteins. E2F^TD represents the E2F transactivation domain. E2F^MB–DP^MB represents the marked box domains of E2F and its heterodimer partner DP. C Models demonstrating the impacts of various phosphorylation events on pRb structural alteration and on its association with E2F and LXCXE motif containing proteins. Only part of the pRb protein regions is shown for illustration. (i) T821/T826 phosphorylation promotes binding of pRbC^N to the pocket domain and inhibits pRb binding to LXCXE motif containing proteins as well as binding to E2F^MB–DP^MB. (ii) S608/S612 phosphorylation partially impedes E2F^TD interaction via promoting association of pRbPL with the pocket domain. (iii) T356/T373 phosphorylation partially blocks E2F^TD binding to pRb and pRb interacting with LXCXE motif containing proteins by inducing pRbN docking on the pocket domain. (iv) S788/S795 and S807/S811 phosphorylation facilitates intramolecular association between the pRbC and the pocket domain to obstruct the sites for E2F^TD and E2F^MB–DP^MB binding