Analysis of cell-cycle regulatory linear motifs bound by the pRb retinoblastoma tumor suppressor

LANG, BENJAMIN; GIBSON, T.J.; SHARAN, MALVIKA; CHEMES, L.; BABU MADAN M

Buenos Aires

Conferencia; ISCB Latin American Meeting; 2016

ISCB and A2B2C

Linear motifs are key elements of regulatory protein interaction networks. Motif gain and losscan modify network topology, and motif affinity determines binding hierarchy. Viruses take advantageof this by evolving linear motifs that hijack and disrupt the host network. Therefore, identifyingrelevant linear motifs and their binding strength is central to understanding host regulation and viralpathogenesis. However, the degenerate nature of linear motifs makes their identification challenging.The pRb retinoblastoma tumor suppressor protein is a central cell-cycle regulator inactivated in humancancer and targeted by carcinogenic viruses including Human Papillomavirus and Merkel cellPolyomavirus. Many pRb interactions are mediated by the LxCxE motif, present in host and viralproteins. In this study, we undertook a comprehensive analysis of pRb-binding LxCxE motifs in orderto improve our ability to identify binders and our understanding of the RB1 interaction network.