The DEK oncoprotein and its emerging roles in gene regulation

Sandén, Carl; Gullberg, Urban

doi:10.1038/leu.2015.72

Cited by 34 publications

(31 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,9 The DEK gene encodes a DNAbinding protein that regulates multiple chromatin-related processes such as transcription, replication, splicing, and DNA repair. 10,11 DEK is preferentially expressed in actively proliferating and malignant cells, and its function is closely related to many human diseases. 12 For example, it functions as an autoantigen in multiple autoimmune diseases, such as juvenile rheumatoid arthritis, and systemic lupus erythematosus.…”

Section: Introductionmentioning

confidence: 99%

DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis

Feng

Liu

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Astrocytic tumors are the most common neuroepithelial neoplasms with high relapse rate after surgery. Understanding the molecular mechanisms for astrocytic tumorigenesis and progression will lead to early diagnosis and effective treatment of astrocytic tumors. The DEK mRNA and protein expression in normal brain tissues and astrocytic tumors was quantified. To investigate DEK functions in tumor cells, DEK gene was silenced with siRNA in U251 glioblastoma cells. Cell proliferation, cell cycle and apoptosis were then measured. The expression and activity of key genes that regulate cell proliferation and apoptosis were also measured. We identified DEK as a high expressed gene in astrocytic tumor tissues. DEK expression level was positively correlated with the pathological grade of astrocytic tumors. Gene silencing of DEK in U251 glioblastomas inhibited cell proliferation and blocked cells at G0/G1 phase of cell cycle. DEK depletion also induced cell apoptosis, with up-regulated expression of P53 and P21 and down-regulated expression of Bcl-2 and C-myc. The Caspase-3 activity in U251 cells was also significantly increased after knockdown. Our results provided evidences that DEK regulates proliferation and apoptosis of glioblastomas. DEK gene silencing may induce apoptosis through P53-dependent pathway. Our data indicated DEK plays multiple roles to facilitate tumor growth and maintenance. It can be used as a potential target for astrocytic tumor diagnosis and gene therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis

Feng

Liu

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

show abstract

“…Although DEK bears little resemblance to other proteins, DEK does contain a conserved region called the Saf/Actinus/PARP-box (SAP-box) that has a helix-turn-helix motif that binds to DNA [22] further facilitated by a second DNA binding structure found in the C-terminal end of the protein [22, 23**]. There is some debate on how DEK recognizes where to bind to DNA.…”

Section: Intracellular and Extracellular Dek Functionsmentioning

confidence: 99%

“…There is some debate on how DEK recognizes where to bind to DNA. Either DEK functions by binding to specific DNA structures or in a sequence-dependent manner [23**] since DEK both accumulates onto specific chromatin structures (such as four-way DNA junctions [24]) and to sequence-specific areas (such as TG-rich peri-ets sites of HIV-2 enhancer regions [25]). However, there remains some controversy on whether DEK recognizes specific DNA sequences as DEK has been shown to non-discriminately bind to DNA of various sequences in the absence of other proteins [26, 27].…”

Section: Intracellular and Extracellular Dek Functionsmentioning

confidence: 99%

“…The later findings were further supported by the fact that DEK associates with heterochromatin binding protein (HP)1α allowing for binding to H3K9me 3 and the chromatin remodeling complex B-WICH, both involved in the replication and stabilization of heterochromatin [29, 33]. Information on the role of DEK in gene regulation is reviewed in detail in Sanden and Gulberg, 2015 [23**]. …”

Section: Intracellular and Extracellular Dek Functionsmentioning

confidence: 99%

See 1 more Smart Citation

A role for intracellular and extracellular DEK in regulating hematopoiesis

Capitano

Broxmeyer

2017

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of review Hematopoietic stem/progenitor cell fate decision during hematopoiesis is regulated by intracellular and extracellular signals such as transcription factors, growth factors, and cell-to-cell interactions. In this review we explore the function of DEK, a nuclear phosphoprotein, on gene regulation. We also examine how DEK is secreted and internalized by cells, and discuss how both endogenous and extracellular DEK regulates hematopoiesis. Finally, we explore what currently is known about the regulation of DEK during inflammation. Recent findings DEK negatively regulates the proliferation of early myeloid progenitor cells but has a positive effect on the differentiation of mature myeloid cells. Inflammation regulates intracellular DEK concentrations with inflammatory stimuli enhancing DEK expression. Inflammation-induced NF-κB activation is regulated by DEK, resulting in changes in the production of other inflammatory molecules such as IL-8. Inflammatory stimuli (i.e. DEK) in turn regulates DEK secretion by cells of hematopoietic origin. However, how inflammation-induced expression and secretion of DEK regulates hematopoiesis remains unknown. Summary Understanding how DEK regulates hematopoiesis under both homeostatic and inflammatory conditions may lead to a better understanding of the biology of HSCs and HPCs. Furthering our knowledge of the regulation of hematopoiesis will ultimately lead to new therapeutics that may increase the efficacy of hematopoietic stem cell transplantation.

show abstract

“…However, in patients SPOP has a missense mutation in its substrate binding domain causing it not bind to SRC-3 and stabilizing SRC-3 [86, 87]. When SPOP is found mutated, DEK a SPOP substrate and onco-protein [88], was found to be up-regulated and contributed to tumor cell invasion [89]. …”

Section: Mechanisms That Confer Resistance To Anti-androgen Therapymentioning

confidence: 99%

The importance of non-nuclear AR signaling in prostate cancer progression and therapeutic resistance

Zarif

Miranti

2016

Cellular Signalling

View full text Add to dashboard Cite

The androgen receptor (AR) remains the major oncogenic driver of prostate cancer, as evidenced by the efficacy of androgen deprivation therapy (ADT) in naïve patients, and the continued effectiveness of second generation ADTs in castration resistant disease. However, current ADTs are limited to interfering with AR ligand binding, either through suppression of androgen production or the use of competitive antagonists. Recent studies demonstrate 1) the expression of constitutively active AR splice variants that no longer depend on androgen, and 2) the ability of AR to signal in the cytoplasm independently of its transcriptional activity (non-genomic); thus highlighting the need to consider other ways to target AR. Herein, we review canonical AR signaling, but focus on AR non-genomic signaling, some of its downstream targets and how these effectors contribute to prostate cancer cell behavior. The goals of this review are to 1) re-highlight the continued importance of AR in prostate cancer as the primary driver, 2) discuss the limitations in continuing to use ligand binding as the sole targeting mechanism, 3) discuss the implications of AR non-genomic signaling in cancer progression and therapeutic resistance, and 4) address the need to consider non-genomic AR signaling mechanisms and pathways as a viable targeting strategy in combination with current therapies.

show abstract

The DEK oncoprotein and its emerging roles in gene regulation

Cited by 34 publications

References 70 publications

DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis

DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis

A role for intracellular and extracellular DEK in regulating hematopoiesis

The importance of non-nuclear AR signaling in prostate cancer progression and therapeutic resistance

Contact Info

Product

Resources

About