c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signaling

Thank you again for submitting your manuscript for consideration by The EMBO Journal. It has now been seen by three expert reviewers, whose comments are copied below. As you will see, they all consider your results as a first implication of K11-linked ubiquitin chains in TNF signaling interesting and potentially important and thus in principle suited for publication in The EMBO Journal. Nevertheless, they also all raise a number of major as well as more specific issues with the manuscript in its current form. While I do not feel that all of them will necessarily have to be addressed through further experiments to warrant successful further consideration, one point raised especially by referees 2 and 3 will however be very important, which is to provide stronger and more direct evidence for the actual involvement/importance of K11-linked chains in TNF/NF-kB signaling. On the other hand, some of the more specific points (such as extending certain experiments also to homologs/paralogs) that would round up the analysis may not be strictly required, unless of course unraveling potential redundancies might help in uncovering the physiological significance of the TNF-induced K11 chains as mentioned above.