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  • Review Article
  • Published:

Id family of helix-loop-helix proteins in cancer

An Erratum to this article was published on 01 September 2005

Key Points

  • Inhibitor of DNA binding (Id) family members are key regulatory proteins in a wide range of developmental and cellular processes and function by inhibiting target proteins that include the basic helix-loop-helix transcription factors, members of the Ets protein family and retinoblastoma.

  • Ids serve as downstream targets of known oncogenic pathways. However, the characterization of Id expression in human tumours and mouse models of cancer requires more careful analysis.

  • Ids can contribute to tumorigenesis by inhibiting cell differentiation, stimulating proliferation and facilitating tumour neoangiogenesis.

  • Id overexpression might mimic the activity of other oncogenes or the loss of tumour suppressor activity.

  • The low postnatal expression of the Ids and their roles in tumorigenesis and tumour neoangiogenesis mark them as attractive targets for anti-cancer therapy.

Abstract

Over the past few decades, biologists have identified key molecular signatures associated with a wide range of human cancers. Recently, animal models have been particularly useful in establishing whether such signatures have functional relevance; the overexpression of pro-oncogenic or loss of anti-oncogenic factors have been evaluated for their effects on various tumour models. The aim of this review is to analyze the potential role of the inhibitor of DNA binding (Id) proteins in cancer and examine whether deregulated Id activity is tumorigenic and contributes to hallmarks of malignancy, such as loss of differentiation (anaplasia), unrestricted proliferation and neoangiogenesis.

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Figure 1: Cell fate determination by Id proteins.
Figure 2: Cell-cycle regulation involving Id proteins.
Figure 3: Role of Id proteins in peripheral and bone-marrow-derived endothelial cells.

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Correspondence to Robert Benezra.

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DATABASES

Entrez Gene

BRCA1

CDK2

p16

p21

p27

ELSPBP1

ETS1

ID1

ID2

ID3

ID4

MAX

RB

TAL1

TCF12

TCF4

Cancer.gov

breast cancer

cervical cancer

colon cancer

endometrial cancer

Ewing's sarcoma

gastric cancer

leukaemia

liver cancer

melanoma

ovarian cancer

pancreatic cancer

pheochromocytomas

prostate cancer

rectal cancer

seminoma

thyroid cancer

FURTHER INFORMATION

Benezra laboratory homepage

Zymed Laboratories

Glossary

EPHRUSSI (E)-BOX

The Ephrussi box (E-box), is a hexameric DNA consensus sequence that is characterized by the consensus CANNTG, an example being CACGTG bound by the E-box-binding transcription factor MYC.

NEURAL CREST

The neural crest comprises a bilaterally paired strips of cells that arise in the ectoderm at the margins of the neural tube. These cells migrate to many locations and differentiate into many cell types within the embryo.

FLOXED

Refers to a DNA construct in which a gene or gene segment is flanked by loxP sites in the same orientation; Cre recombinase excises the segment between the loxP sites.

MORPHOLINO ANTISENSE

Morpholino antisense oligonucleotides are assembled from four different morpholino subunits, each of which contain one of the four genetic bases (A, C, G and T) linked to a six-membered morpholine ring. Eighteen to 25 subunits of these four subunit types are joined in a specific order by non-ionic phosphorodiamidate intersubunit linkages to give a morpholino oligonucleotide.

NEUROECTODERM

Ectoderm on the dorsal surface of the early vertebrate embryo that gives rise to the cells (neurons and glia) of the nervous system. Also called the neural plate.

SV40 TAG

The simian virus 40 large T antigen that binds both p53 and RB, suppressing their function.

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Perk, J., Iavarone, A. & Benezra, R. Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer 5, 603–614 (2005). https://doi.org/10.1038/nrc1673

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