IQ Motif Containing GTPase Activating Proteins (IQGAPs), A-Kinase Anchoring Proteins (AKAPs) and Kinase Suppressor of Ras Proteins (KSRs) in Scaffolding Oncogenic Pathways and Their Therapeutic Potential.
Talina MohapatraManjusha DixitPublished in: ACS omega (2022)
Scaffolding proteins colocalize interacting partners on their surface and facilitate complex formation. They have multiple domains and motifs, which provide binding sites for various molecules. This property of scaffolding proteins helps in the orderly transduction of signals. Abnormal signal transduction is frequently observed in cancers, which can also be attributed to the altered functionality of scaffolding proteins. IQ motif containing GTPase activating proteins (IQGAPs), kinase suppressor of Ras (KSR), and A-kinase anchoring proteins (AKAPs) tether oncogenic pathways RAS/RAF/MEK/ERK, PI3K/AKT, Hippo, Wnt, and CDC42/RAC to them. Scaffolding proteins are attractive drug targets as they are the controlling hub for multiple pathways and regulate crosstalk between them. The first part of this review describes the human scaffolding proteins known to play a role in oncogenesis, pathways altered by them, and the impact on oncogenic processes. The second part provides information on the therapeutic potential of scaffolding proteins and future possibilities. The information on the explored and unexplored areas of the therapeutic potential of scaffolding proteins will be equally helpful for biologists and chemists.