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Table 2 Mechanisms of increased IGF-2 gene/protein activities

From: The Role of Insulin-Like Growth Factor 2 and Its Receptors in Human Tumors

Normally IGF-2 is expressed from the paternal allele with the Maternal allele being transcriptionally silent (imprinting) (75).
Loss or imprinting (LOI)
Maternal allele becomes re-imprinted; transcription occurs from two IGF-2 alleles (23–26,77–91).
Loss of heterozygosity (LOH)
LOH is associated with duplication of the active paternal IGF-2 allele; transcription occurs from two IGF-2 alleles leading to higher mRNA level (9398).
Altered binding proteins
Cleavage of IGF BPs by binding protein-specific proteases increase IGF-2 activity (69,100102).
Loss of transcriptional suppressor protein
Suppressor proteins (WT-1, p53, and possibly CTCF), which bind to sequences in the IGF-2 enhancer/promoter regions, prevent transcription of IGF-2; when absent or mutated IGF-2 gene transcription increases (104108).
Activation of transcription factors
Those that positively regulate IGF-2 (104108).
Altered IGF-2 receptor/mannose-6-phosphate
Mutation in IGF-2 binding site required for the degradation of the IGF-2 decreases IGF-2 bioavailability (5764).
  1. For details see reference 76.