The helix–loop–helix protein ID1 localizes to centrosomes and rapidly induces abnormal centrosome numbers

Hasskarl, Jens; Duensing, Stefan; Manuel, Edwin R.; Münger, Karl

doi:10.1038/sj.onc.1207310

Cited by 41 publications

(56 citation statements)

References 63 publications

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“…Centrosomal localization of S5A was substantiated by colocalization of the S5A-signal with the centrosome markers g-tubulin ( Figure 3a) and pericentrin (Figure 3b). Further analyses revealed centrosomal S5A staining throughout the cell division cycle (Figure 3 and Supplementary Figures 2 and 3), similar to that reported for ID1 (Hasskarl et al, 2004). Due to technical limitations we were not able to perform triple staining for centrosomes, ID1 and S5A, but we detected co-localization of endogenous S5A and ID1 to cytoplasmic dots, which presumably represent centrosomes (Figure 3c).…”

Section: S5a Expression Does Not Affect Induction Of Centrosome Abnorsupporting

confidence: 79%

“…A direct role of ID proteins in tumor development has been suspected, especially for ID1, as it is frequently overexpressed in human malignancies, and in some cases high expression has been linked to unfavorable clinical outcome (reviewed in Perk et al, 2005). ID1, but not ID2, ID3 or ID4, may contribute to oncogenesis by subverting centrosome duplication (Hasskarl et al, 2004). Here, we show that the ability of ID1 to cause centrosome abnormalities correlates with its ability to associate with proteasome subunit S5A, and that ectopic expression of S5A can reverse ID1-mediated centrosomal abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…HeLa, U2OS and HaCaT cells were maintained in Dulbecco's minimal eagel's media (DMEM) with 10% fetal bovine serum, Saos-2 cells in DMEM with 20% FBS, containing penicillin (50 U ml À1 ), streptomycin (50 mg ml À1 ) and glutamine (2 mM). (N-terminal HA-tag), pFLAG, pFLAG-Dest (N-terminal FLAG-tag), pID1-wt-FLAG, pID1-V98G-FLAG, pID1-DNH2-FLAG and pID1-DCOOH-FLAG (Hasskarl et al, 2004). ID1 cDNA was digested with MaeII to remove the HLH-domain.…”

Section: Cell Culturementioning

confidence: 99%

“…We have shown previously that a fraction of ID1 localizes to centrosomal structures, and that forced expression of ID1 can lead to rapid overduplication of centrosomes (Hasskarl et al, 2004). Centrosomes consist of a pair of centrioles surrounded by pericentriolar material.…”

Section: Introductionmentioning

confidence: 99%

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Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

2007

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The inhibitor of DNA-binding (ID) proteins are dominantnegative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. High-level expression of some ID family members has been observed in human malignancies, and in some cases was correlated with poor clinical prognosis. Ectopic ID1 expression extends the life span of primary human epithelial cells, inhibits cellular differentiation and induces centrosome duplication errors, thus suggesting that ID1 may have oncogenic activities. ID1 can bind to the proteasomal subunit S5A/Rpn10, but the biological consequences of the interaction have not been studied in detail. Here, we show that ID1's ability to induce supernumerary centrosomes correlates with S5A binding. Similar to ID1, a fraction of the S5A protein localizes to centrosomal structures. Furthermore, partial depletion of S5A by RNA interference causes accumulation of cells with supernumerary centrosomes. These results are consistent with the model that ID1 dysregulates centrosome homeostasis at least in part by interfering with S5A activities at the centrosome.

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Section: S5a Expression Does Not Affect Induction Of Centrosome Abnorsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

2007

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“…22 Interestingly, ID1, but not other ID proteins (ID2, ID3 and ID4), is localized at centrosome and forced expression of ID1 results in accumulation of supernumerary centrosomes, [37][38][39] suggesting that stabilization of ID1 through USP1 overexpression can induce centrosome amplification. To explore this possibility, we generated NIH3T3 cells stably transduced with Id1 and compared the induction of centrosome amplification with wt-Usp1 NIH3T3 cells (Fig.…”

Section: Usp1-induced Centrosome Amplification Results In Chromosome mentioning

confidence: 99%

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

2016

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Defects in the regulation of centrosome duplication lead to tumorigenesis through abnormal cell division and resulting chromosome missegregation. Therefore, maintenance of accurate centrosome number is critical for cell fate. The deubiquitinating enzyme USP1 plays important roles in DNA repair and cell differentiation. Importantly, increased levels of USP1 are detected in certain types of human cancer, but little is known about the significance of USP1 overexpression in cancer development. Here we show that Usp1 plays a novel role in regulating centrosome duplication. The ectopic expression of wild-type Usp1, but not C90S Usp1 (catalytically inactive mutant form), induced centrosome amplification. Conversely, ablation of Usp1 in mouse embryonic fibroblasts (MEFs) showed a significant delay in centrosome duplication. Moreover, Usp1-induced centrosome amplification caused abnormal mitotic spindles, chromosome missegregation and aneuploidy. Interestingly, loss of inhibitor of DNA binding protein 1 (ID1) suppressed Usp1-induced centrosome amplification. Taken together, our results strongly suggest that Usp1 is involved in the regulation of centrosome duplication, at least in part via ID1, and Usp1 may exert its oncogenic activity, partially through inducing centrosome abnormality.

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ID1‐, ID2‐, and ID3‐regulated gene expression in E2A positive or negative prostate cancer cells

2007

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The overall effect of Id proteins on proliferation and apoptosis is independent of E-proteins. E-proteins can however determine the magnitude of response or in some cases even reverse the Id-mediated target gene expression. Evaluating E-protein expression in conjunction with Id proteins will allow better understanding of the molecular mechanism of action of Id proteins and increase their prognostic significance in PCA.

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The helix–loop–helix protein ID1 localizes to centrosomes and rapidly induces abnormal centrosome numbers

Cited by 41 publications

References 63 publications

Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

ID1‐, ID2‐, and ID3‐regulated gene expression in E2A positive or negative prostate cancer cells

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