Inhibitor of DNA Binding Proteins in Tumours - Therapeutic Strategies in Cancer Biology and Pathology - page 176

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Inhibitor of DNA Binding
Proteins in Tumours

Inhibitor of DNA binding proteins (IDs1-4) are dominant negative bHLH transcrip-
tion factors. These ID bHLH proteins lack the basic DNA binding domain and so
have no DNA binding ability but they do heterodimerise with and negatively regu-
late the activity of other bHLH transcription factors, by sequestering and preventing
DNA binding by the target transcription factor.
As transcription factors IDs are involved in the regulation of several signalling
pathways that determine many biological functions including cell proliferation, dif-
ferentiation, neurogenesis, myogenesis and differentiation (see Morgenstern and
Atchley, 1999; Norton et al., 1998). Salient biological properties are summarised in
Table 30.1 .

Table 30.1 ID bHLH Proteins and Their Biological Properties

ID Synonyms Chromosome

Location

Biological Properties

ID1 bHLHb24 20q11 EGR→ID1 cell proliferation;

inhibits NF-κB and apoptosis;
CSC maintenance; invasion;
angiogenesis; Parallel↑EGFR;
VEGF?

ID2 bHLHb26 2p25 EGR2→ID2; inhibits RANKL/

NF-κB→ inhibits apoptosis;
CSC maintenance; angiogenesis;
Parallel↑EGFR; VEGF?

ID3 HEIR-1, bHLHb25 1p36.13-p36.12 CSC maintenance

Angiogenesis; Parallel↑EGFR;
VEGF?

ID4 bHLHb27 6p22.3 Tumour and growth suppression;

stem cell programme;
Cdc42→ID4↓
ID4→BRCA1↓; angiogenesis?

Source : Information based on Human Gene Nomenclature Committee and references cited in the text.