SCF ubiquitin ligase-targeted therapies.
The clinical successes of proteasome inhibitors for the treatment of cancer have highlighted the therapeutic potential of targeting this protein degradation system. However, proteasome inhibitors prevent the degradation of numerous proteins, which may cause adverse effects. Increased specificity could be achieved by inhibiting the components of the ubiquitin-proteasome system that target specific subsets of proteins for degradation. F-box proteins are the substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes. Through the degradation of a plethora of diverse substrates, SCF ubiquitin ligases control a multitude of processes at the cellular and organismal levels, and their dysregulation is implicated in many pathologies. SCF ubiquitin ligases are characterized by their high specificity for substrates, and these ligases therefore represent promising drug targets. However, the potential for therapeutic manipulation of SCF complexes remains an underdeveloped area. This Review explores and discusses potential strategies to target SCF-mediated biological processes to treat human diseases.
1] Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA. [2].
Jeffrey R
JR
Skaar
1] Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA. [2].
Julia K
JK
Pagan
1] Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA. [2] Howard Hughes Medical Institute.
Michele
M
Pagano
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D044783:F-Box Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D044843:SKP Cullin F-Box Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000970:Antineoplastic Agents; D044783:F-Box Proteins; D044843:SKP Cullin F-Box Protein Ligases