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. 2017 Dec 26;9(5):6282–6297. doi: 10.18632/oncotarget.23676

Figure 7. A diagram showing the interplay between LIMD1 and LMP1.

Figure 7

LMP1 induces LIMD1 expression via NFκB and IRF4 axes. In turn, LIMD1 participates in LMP1 signal transduction by interacting with TRAF6. LIMD1 protects EBV-transformed cells from DNA damage through inducing p62-mediated autophagy that plays a crucial role in DNA repair in cancers, and this function may or may not depend on LMP1 signaling in that LIMD1 may be regulated and promotes DNA repair through other LMP1-independent mechanisms. LMP1 may induce autophagy through distinct but not fully understood mechanisms, one of which involves p62 that is likely induced by LMP1/NFκB. The pathways with broken lines represent several possible LMP1-dependent and -independent mechanisms underlying EBV regulation of p62-mediated autophagy, and are under our investigation. ① LIMD1 participates in LMP1 signal transduction to NFκB activation and ROS production, both of which induce p62; ② Other EBV factors may indirectly induce p62 expression; for example, EBNA1 and EBNA2 produce ROS that is able to induce p62; ③ LIMD1 inhibits expression of Bim that is known to inhibit p62-mediated autophagy; ④ p62 interacts with LIMD1 and TRAF6 in a multi-protein complex that facilitates NFκB activation in diverse contexts, and this mechanism may also function in LMP1 activation of NFκB; ⑤ LIMD1 may regualte p62-mediated autophagy through other LMP1-independent strategies.