Structural Insights into Ankyrin Repeat-Containing Proteins and Their Influence in Ubiquitylation

Round 1

Reviewer 1 Report

Excellent review. I wish you would have a section on targeting Ankyrin repeat-containing protein therapeutics.

Author Response

We thank the reviewer for sharing our enthusiasm on this topic.  We appreciate the reviewer's suggestion of including another section discussing the potential of targeting Ankyrin repeat-containing proteins for therapeutics.  Since this is new area of study with very little currently reported in the literature on this topic, we are hesitant to include a new section at this time.

We also thank the reviewer for pointing out that there were some grammatical errors in our review.  We have carefully proofread our paper and made corrections to address this.

Reviewer 2 Report

The authors address a topic of great interest to the scientists working in the field of proteomics focused on the studies of protein-protein interactions, from basic research to drug development. The Ankyrin Repeat (AR) is one of the most frequently observed amino acid motifs in many proteins. This protein-protein interaction domain is involved in a diverse set of important cellular functions including cell and cell-cell signaling, cytoskeleton integrity, transcription, inflammatory response and the ubiquitylation signaling pathways. Importantly, defects in the AR domains of many proteins have been found in a number of human diseases including cancer and neurological diseases. The presence of such overviews in the literature is limited, especially the papers describing and discussing the relationships between the structure of the AR domains in the key AR-containing proteins and the roles they play in ubiquitylation and the cascading pathways that follow upon modification of specific substrates in these processes. In my opinion this is a well-written and constructed manuscript describing in details all important topic issues with the high level of comments and discussions. The readers of the International Journal of Molecular Sciences should find the review interesting.

Author Response

We thank the reviewer for sharing our enthusiasm on this topic and we appreciate their positive comments about our review.