One for all and all for one: RB defends the cell while IDE, PTEN and IGFBP-7 antagonize insulin and IGFs to protect RB.
Tumor suppressor proteins are the main cellular barrier opposing neoplastic transformation. Among these host molecules, retinoblastoma protein (RB) plays a central role. A novel insight is now advanced to suggest that various inhibitors of insulin and insulin-like growth factor (IGF) signalling such as the putative tumor suppressor insulin-degrading enzyme (IDE) as well as the anti-oncogenic proteins PTEN and insulin-like growth factor-binding protein 7 (IGFBP-7) serve the common goal of ensuring that RB remains active. Since, moreover, IDE and IGFBP-7 each potentially achieves RB protection through preventing both binding and inactivation of RB by insulin, IGF-1 or IGF-2, the present perception also vindicates the importance of previous findings on the physical interaction of any of these growth factors with RB for cell fate. Notably, the therapeutic counterpart of this natural principle for maintaining or restoring RB function through insulin/IGF neutralization is the innovative class of anti-cancer agents termed MCR peptides and developed over the past decade.
Radulescu
Razvan T
RT
Molecular Concepts Research, Munich, Germany. ratura@gmx.net
D049109:Cell Proliferation; D002470:Cell Survival; D019610:Cytoprotection / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007339:Insulysin / Q000378:metabolism*; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D016160:Retinoblastoma Protein; D013002:Somatomedins; C102529:insulin-like growth factor binding protein-related protein 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D007339:Insulysin