About this Research Topic
Protein ubiquitination is one of the critical post-translational modifications of proteins. The process is mediated by the highly-conserved ATP-dependent E1/E2/E3 enzymatic reactions. The ubiquitinated proteins are then subjected to the proteasomal or lysosomal degradations, or they acquire novel molecular functions (non-degradation) according to their “ubiquitin codes”. Dysfunction of protein ubiquitination causes a variety of severe human diseases (e.g. cancers, neurodegenerative diseases, autoimmune diseases).
Cullin-3 (CUL3) is a scaffold protein of the cullin/RING-type E3 ligase (CRL) complex. The initiation of the CUL3-mediated ubiquitination is neddylation (the conjugation of a ubiquitin-like protein, Nedd8) at K712 position of CUL3. Then, activated CUL3 recruits target substrate proteins through the substrate recognition receptors, called BTB proteins (BTBPs). Human genome encodes 183 BTBPs, and thus this large numbers of BTBPs generate a diversity of ubiquitinated substrates in the CUL3-mediated ubiquitination system.
Research of the CUL3/BTBP biology have uncovered patho-physiological functions of each BTBP together with the identification of their ubiquitinated substrates. The cellular functions of the CUL3/BTBP/substrate axes are essentially and extremely divergent among cell types (e.g. cell cycle, membrane trafficking, signal transduction, transcription, cytoskeletal regulation, epigenetics). Physiologically, CUL3 is essential for embryonic development and angiogenesis. From the clinical standpoints, mutations in BTBPs have been identified in several cancers (SPOP in prostate/endometrial cancers, KBTBD4 in medulloblastoma).
Accordingly, the understanding of history and front line of the CUL3/BTBP research is essential for building of new hypothesis, concepts and ideas. The elucidation of novel patho-physiological roles of BTBPs as well as identification of their ubiquitinated substrates would expand this research field.
The aim of this Research Topic is to highlight the recent progress of the CUL3/BTBP research and address the open questions around the CUL3/BTBP-dependent molecular mechanisms. Our topic will contribute to understanding of the CUL3/BTBP biology, leading to the establishment of new pharmaceutical targets and development of novel clinical applications.
The submission of Original Research, Review, Mini Review, and Perspective articles that cover, but are not limited to, the following subtopics will be encouraged:
• Cellular functions of the CUL3/BTBP/substrate axes in various cell lines
• Physiological roles of the CUL3/BTBP/substrate axes in animal models (e.g. angiogenesis)
• Pathological roles of the CUL3/BTBP/substrate axes in animal models (e.g. tumorigenesis)
• Mutations in CUL3 and BTBPs: importance in diagnosis, prognosis and treatment for human diseases.
• Tools and methodology for the identification of target ubiquitinated substrates by the CUL3/BTBPs
• Development of new pharmacological agents (inhibitors and activators) that target the CUL3/BTBP/substrate protein complex for therapy of human diseases
• Spatio-temporal regulation of intracellular distribution of the CUL3/BTBP/substrate protein complex
• Neddylation cycle of CUL3
• Development of new pharmacological agents that target neddylation or deneddylation of CUL3
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
