The roles of EPIYA sequence to perturb the cellular signaling pathways and cancer risk

Abstract It was shown that several pathogenic bacterial effector proteins contain the Glu-Pro-Ile-Tyr-Ala (EPIYA) or a similar sequence. These bacterial EPIYA effectors are delivered into host cell via type III or IV secretion system, where they undergo tyrosine phosphorylation at the EPIYA sequences, which triggers interaction with multiple host cell SH2 domain-containing proteins and thereby manipulate host cell signaling for more effective infection. Recently, it was also shown that several mammalian proteins contain EPIYA sequences. Tyrosine phosphorylation at EPIYA sequences enable them to interact with SH2-domain containing proteins specifically. Therefore, it was proposed that the mammalian EPIYA motifs might have been exploited by pathogenic bacteria and they act as pathogenic “Master keys” to perturb multiple signaling pathways through promiscuous binding with SH2 domain-containing proteins. In this regards, it was found that EPIYA motifs in some bacterial effector proteins to be unfolded and they showed structural flexibility features. Up to now, the structure of mammalian host proteins containing EPIYA motifs is not completely understood. In this review, we investigate the roles of functional EPIYA sequences as key sequences in related proteins to perturb cell signal transduction pathways and cancer risk. Key words: EPIYA sequences, Bacterial effector proteins, Host proteins, Cell signaling, Cancer Conflicts of interest: None Funding: None