Id genes and proteins as promising targets in cancer therapy

Fong, Sylvia; Debs, Robert J.; Desprez, Pierre-Yves

doi:10.1016/j.molmed.2004.06.008

Cited by 128 publications

(133 citation statements)

References 57 publications

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“…Accumulating evidence has demonstrated that the expression of Id proteins is significantly correlated with the progression of cancer, and therefore Id proteins are now considered to be oncoproteins (9). Consistent with this notion, expression of Ids is strictly regulated at the transcriptional level (3,6,7), and recent studies have shown that protein degradation is one mechanism of their post-translational regulation (8,15,42).…”

Section: Discussionmentioning

confidence: 89%

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Nucleo-cytoplasmic Shuttling of Id2, a Negative Regulator of Basic Helix-Loop-Helix Transcription Factors

Kurooka

Yokota

2005

Journal of Biological Chemistry

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Id proteins function as negative regulators for basic helix-loop-helix transcriptional factors that play important roles in cell fate determination. They preferentially associate with ubiquitously expressed E proteins of the basic helix-loop-helix family and prevent them from binding to DNA and activating transcription. Although their small size suggests that Id proteins enter and exit the nucleus by passive diffusion, several studies have indicated that other pathways may regulate their subcellular localization. In this study, we obtained evidence that Id2 has the ability to shuttle between the nucleus and the cytoplasm. When passive diffusion was prevented by fusion with green fluorescent protein (GFP), Id2 was predominantly localized in the cytoplasm. Using GFP fusion constructs, we demonstrated that the C-terminal region is required for cytoplasmic localization. Nuclear accumulation of GFP-Id2 in cells treated with the nuclear export inhibitor leptomycin B suggests that the nuclear export receptor chromosome region maintenance protein 1 mediates the cytoplasmic localization of Id2. Id2 contains two putative leucine-rich nuclear export signals, and the nuclear export signal in the Cterminal region is essential for nuclear export. On the other hand, the helix-loop-helix domain is important for nuclear localization. Finally, experiments using reporter assays revealed an inverse correlation between nuclear export and transcriptional repression via the E-box sequence. Based on all these findings, we propose that nucleo-cytoplasmic shuttling is a novel mechanism for the regulation of Id2 function.

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Section: Discussionmentioning

confidence: 89%

“…The functions of Ids are strictly regulated at levels of transcription (6,7) and protein stability (8). Recent studies have revealed additional roles for these proteins in apoptosis, cellular senescence, and tumorigenesis (2,9,10).…”

mentioning

confidence: 99%

Nucleo-cytoplasmic Shuttling of Id2, a Negative Regulator of Basic Helix-Loop-Helix Transcription Factors

Kurooka

Yokota

2005

Journal of Biological Chemistry

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“…Expression of ID1 is indispensable for normal embryonic neuronal development and angiogenesis (Lyden et al, 1999). ID1 is frequently overexpressed in human cancer and associated with aggressive tumor phenotypes (Fong et al, 2004). Repression of ID1 decreased the growth of early tumors in animal models (Lyden et al, 1999;Lasorella et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

et al. 2012

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“…The Id-1 gene (inhibitor of differentiation and DNA binding), a member of the helix-loop-helix transcription factor family, has multiple functions, including inhibition of differentiation, induction of proliferation and delaying replicative senescence (Fong et al, 2004;Sikder et al, 2003). Moreover, Id-1 has been suggested as a potential oncogene, because it is upregulated in many types of human cancer such as breast, prostate and cervical (Lin et al, 2000;Schindl et al, 2001;Ouyang et al, 2002).…”

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confidence: 99%

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

et al. 2008

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High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis. In this investigation, we examined the presence of highrisk HPVs (16, 18, 31, 33 and 35) and the expression of their E6 onco-protein as well as their correlation with Id-1 gene expression, using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis, respectively, in a cohort of 113 Syrian breast cancer patients. We found that high-risk HPV types 16, 18, 31, 33 and 35 are present in 8.84, 9.73, 7.07, 55.75 and 37.16% of our samples, respectively, which represent invasive breast cancers. Overall, 69 (61.06%) of the 113 samples are HPV positive; among these specimens 24 tissues (34.78%) are coinfected with more than one HPV type. Furthermore, we report that the expression of the E6 onco-protein of these high-risk HPVs is correlated with Id-1 overexpression in the majority of invasive breast cancer tissue samples. Our data suggest that high-risk HPV infections are associated with human breast cancer progression in Syrian women.

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Id genes and proteins as promising targets in cancer therapy

Cited by 128 publications

References 57 publications

Nucleo-cytoplasmic Shuttling of Id2, a Negative Regulator of Basic Helix-Loop-Helix Transcription Factors

Nucleo-cytoplasmic Shuttling of Id2, a Negative Regulator of Basic Helix-Loop-Helix Transcription Factors

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

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