Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.56 (insulin-degrading enzyme)
 737 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:One for all and all for one: RB defends the cell while IDE, PTEN and IGFBP-7 antagonize insulin and IGFs to protect RB. 1747 16

Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.
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PMID:Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: implications for cell proliferation control. 2036 53

Insulin is one of the major metabolic hormones regulating glucose homeostasis in the organism and a key growth factor for normal and neoplastic cells. Work conducted primarily over the past 3 decades has unravelled the presence of insulin in human breast cancer tissues and, more recently, in human non-small cell lung carcinomas (NSCLC). These findings have suggested that intracellular insulin is involved in the development of these highly prevalent human tumors. A potential mechanism for such involvement is insulin's binding and inactivation of the retinoblastoma tumor suppressor protein (RB) which in turn is likely controlled by insulin-degrading enzyme (IDE). This model and its supporting data are collectively covered in this survey in order to provide further insight into insulin-driven oncogenesis and its reversal through future anticancer therapeutics.
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PMID:Intracellular insulin in human tumors: examples and implications. 2145 57