The SET Protein Regulates G2/M Transition by Modulating Cyclin B-Cyclin-dependent Kinase 1 Activity

Canela, Núria; Rodríguez–Vilarrupla, Aina; Estanyol, Josep Marı́a; Dı́az, Carmen; Pujol, María Jesús; Agell, Neus; Bachs, Oriol

doi:10.1074/jbc.m207497200

Cited by 135 publications

(149 citation statements)

References 28 publications

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“…As it can be observed in Figure 5a, growing amounts of GAPDH did not affect cyclin B-cdk1 activity. In contrast, as expected by previous results (Canela et al, 2003), SET inhibited cyclin B-cdk1 activity (Figure 5b). Finally, cyclin B-cdk1 activity was analysed in the presence of a fixed amount of SET (5 mM) and growing levels of GAPDH.…”

Section: Resultssupporting

confidence: 89%

“…As SET protein is a cyclin Bcdk1 inhibitor (Canela et al, 2003), we analysed whether GAPDH could affect this inhibitory activity of SET. Thus, we first checked whether GAPDH alone could affect cyclin B-cdk1 activity.…”

Section: Resultsmentioning

confidence: 99%

“…As SET inhibits cyclin B-Cdk1 activity, we first focused our efforts to explore whether GAPDH could affect the inhibition of cyclin B-Cdk1 activity produced by SET (Canela et al, 2003). Our results indicate that in vitro, GAPDH reverses the inhibitory effect of SET on cyclin B-cdk1 complexes.…”

Section: Discussionmentioning

confidence: 98%

“…This region of SET contains a large acidic domain that has been described to be involved in a number of functions as for instance, DNA replication of adenovirus genome (Nagata et al, 1995) or cyclin B-cdk1 inhibition (Canela et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…It reverses the p21 Cip1 inhibitory effect on cyclin E-cdk2 activity (Estanyol et al, 1999), inhibits cyclin B-cdk1 activity (Kellogg et al, 1995;Canela et al, 2003) and enhances the activity of p35 nck5a -cdk5 (Qu et al, 2002).…”

Section: Introductionmentioning

confidence: 98%

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Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

et al. 2006

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We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts in vitro and in vivo with the protein SET. This interaction is performed through the acidic domain of SET located at the carboxy terminal region. On analysing the functional relevance of SET-GAPDH interaction, we observed that GAPDH reverses in a dose-dependent manner, the inhibition of cyclin Bcdk1 activity produced by SET. Similarly to SET, GAPDH associates with cyclin B, suggesting that the regulation of cyclin B-cdk1 activity might be mediated not only by the interaction of GAPDH with SET but also with cyclin B. To analyse the putative role of GAPDH on cell cycle progression, HCT116 cells were transfected with a GAPDH expression vector. Results indicate that overexpression of GAPDH does not affect the timing of DNA replication but induces an increase in the number of mitosis, an advancement of the peak of cyclin B-cdk1 activity and an acceleration of cell cycle progression. All these results suggest that GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

et al. 2006

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Crosstalk between hnRNP K and SET in ATRA‐induced differentiation in acute promyelocytic leukemia

et al. 2021

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HnRNP K protein is a heterogeneous nuclear ribonucleoprotein which has been proposed to be involved in the leukemogenesis of acute promyelocytic leukemia (APL), as well as in differentiation induced by all‐trans retinoic acid (ATRA). We previously demonstrated a connection between SET and hnRNP K function in head and neck squamous cell carcinoma (HNSCC) cells related to splicing processing. The objective of this study was to characterize the participation of hnRNP K and SET proteins in ATRA‐induced differentiation in APL. We observed higher (5‐ to 40‐fold) levels of hnRNP K and SET mRNA in APL patients at the diagnosis phase compared with induction and maintenance phases. hnRNP K knockdown using short‐hairpin RNA led to cell death in ATRA‐sensitive NB4 and resistant NB4‐R2 cells by apoptosis with SET cleavage. In addition, hnRNP K knockdown increased granulocytic differentiation in APL cells, mainly in NB4‐R2 with ATRA. hnRNP K knockdown had an effect similar to that of treatment with U0126 (an meiosis‐specific serine/threonine protein kinase/ERK inhibitor), mainly in NB4‐R2 cells. SET knockdown in APL cells revealed that apoptosis induction in cells with hnRNP K knockdown occurred by SET cleavage rather than by reduction in SET protein. Transplantation of NB4‐R2 cells into nude mice confirmed that arsenic trioxide (ATO) combined with U0126 has higher potential against tumor progression when compared to ATO. Therefore, hnRNP K/SET and ERK are potential therapeutic targets for both antineoplastic leukemia therapy and relapsed APL patients with ATRA resistance.

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The E3 Ligase TRIM4 Facilitates SET Ubiquitin‐Mediated Degradation to Enhance ER‐α Action in Breast Cancer

et al. 2022

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Estrogen receptor alpha (ER‐α) action is critical for hormone‐dependent breast cancer, and ER‐α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)‐resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER‐α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4‐SET interactions are mediated by the RING and B‐box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48‐linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence‐free survival outcomes in patients with ER‐α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients.

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The SET Protein Regulates G2/M Transition by Modulating Cyclin B-Cyclin-dependent Kinase 1 Activity

Cited by 135 publications

References 28 publications

Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

Crosstalk between hnRNP K and SET in ATRA‐induced differentiation in acute promyelocytic leukemia

The E3 Ligase TRIM4 Facilitates SET Ubiquitin‐Mediated Degradation to Enhance ER‐α Action in Breast Cancer

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