KMT Set7/9 is a new regulator of Sam68 STAR-protein

Vasileva, Elena; Shuvalov, Oleg; Petukhov, Alexey; Fedorova, Olga; Daks, Alexandra; Barlev, Nickolai A.

doi:10.1016/j.bbrc.2020.03.017

Cited by 16 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This points to Set7/9 as a potential tumor suppressor. Along with this notion, studies from several groups including ours also suggest that Set7/9 plays antiproliferative and tumor-protective roles in various cancers (7,15,56,57), including NSCLC (21,58).…”

Section: Discussionsupporting

confidence: 54%

p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

Set7/9 is a lysine-specific methyltransferase, which regulates the functioning of both the histone and non-histone substrates, thereby significantly affecting the global gene expression landscape. Using microarray expression profiling, we have identified several key master regulators of metabolic networks, including c-Myc, that were affected by Set7/9 status. Consistent with this observation, c-Myc transcriptional targets—genes encoding the glycolytic enzymes hexokinase (HK2), aldolase (ALDOB), and lactate dehydrogenase (LDHA)—were upregulated upon Set7/9 knockdown (Set7/9KD). Importantly, we showed the short hairpin RNA (shRNA)-mediated attenuation of Set7/9 augmented c-Myc, GLUT1, HK2, ALDOA, and LDHA expression in non-small cell lung cancer (NSCLC) cell lines, not only at the transcriptional but also at the protein level. In line with this observation, Set7/9KD significantly augmented the membrane mitochondrial potential (MMP), glycolysis, respiration, and the proliferation rate of NSCLC cells. Importantly, all these effects of Set7/9 on cell metabolism were p53-independent. Bioinformatic analysis has shown a synergistic impact of Set7/9 together with either GLUT1, HIF1A, HK2, or LDHA on the survival of lung cancer patients. Based on these evidence, we hypothesize that Set7/9 can be an important regulator of energy metabolism in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 54%

p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, overexpression of SETD7 produced opposite results, and was similar to siRNA knockdown of METTL3 and YTHDF2. Therefore, SETD7 mRNA is downregulated by hMETTL3/DF2 m 6 A to increase the metastatic potential of BlaCa cells, which supports a tumour-suppressing function of SETD7 [34]. The authors backed their findings with analysis of the TCGA data, where SETD7 transcript was lower in BlaCa compared with normal samples, with similar levels between stages 2, 3 and 4 [34].…”

Section: Bladder Cancermentioning

confidence: 83%

“…CRISPR/Cas9 knock-out of SETD7 in HCT116 cells decreased the cytoplasmic Sam68 protein and induced cell accumulation in early S phase and apoptosis. The authors suggested that SETD7 in CRC cells affects Sam68 cell localisation, neutralising its nuclear function [6], although this may also be due to total protein reduction. The authors supported their conclusions by analysis of SETD7 expression in the GSE39582 dataset (443 CRC samples) using the Syntarget tool (bioprofiling.de) to show that high co-expression of SETD7 and KHDRBS1 (Sam68) significantly correlated with better overall survival of CRC patients, while patients with low SETD7 and high KHDRBS1 expression showed poor OS.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…Several other non-histone protein targets of SETD7 have since been identified, including numerous transcription factors and epigenetic regulators (reviewed in [3,4]). Methylation by SETD7 modulates protein stability [5], subcellular localisation [6,7], and/or interactions with other proteins [8]. In some cases, methylation by SETD7 competes with other posttranslational modifications to activate or inhibit target protein function [3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Review to Define the Multi-Faceted Role of Lysine Methyltransferase SETD7 in Cancer

Monteiro

Williams

Helguero

2022

Cancers

View full text Add to dashboard Cite

Histone–lysine N-methyltransferase SETD7 regulates a variety of cancer-related processes, in a tissue-type and signalling context-dependent manner. To date, there is no consensus regarding SETD7´s biological functions, or potential for cancer diagnostics and therapeutics. In this work, we summarised the literature on SETD7 expression and function in cancer, to identify the contexts where SETD7 expression and targeting can lead to improvements in cancer diagnosis and therapy. The most studied cancers were found to be lung and osteosarcoma followed by colorectal and breast cancers. SETD7 mRNA and/or protein expression in human cancer tissue was evaluated using public databases and/or in-house cohorts, but its prognostic significance remains inconclusive. The most studied cancer-related processes regulated by SETD7 were cell proliferation, apoptosis, epithelial-mesenchymal transition, migration and invasion with special relevance to the pRb/E2F-1 pathway. SETD7 consistently prevented epithelial to mesenchymal transition in different cancer types, and inhibition of its function appears to be associated with improved response to DNA-damaging agents in most of the analysed studies. Stabilising mutations in SETD7 target proteins prevent their methylation or promote other competing post-translational modifications that can override the SETD7 effect. This indicates that a clear discrimination of these mutations and competing signalling pathways must be considered in future functional studies.

show abstract

“…However, there is a growing volume of evidence suggesting that MORN repeats may mediate proteinprotein interactions [24,25]. Indeed, by using a GST-pull-down assay coupled with mass spectrometry, we have demonstrated that MORN repeats are responsible for the majority of SET7/9 interactions [10]. The resolved crystal structure of the SET domain revealed that the amino-terminal domain has a groove running across the extended beta sheet to the SET domain leading to a narrower channel running around the SET domain [27].…”

Section: The Structural Organization Of Set7/9 Methyltransferasementioning

confidence: 94%

The Role of Lysine Methyltransferase SET7/9 in Proliferation and Cell Stress Response

Daks

Vasileva

Fedorova

et al. 2022

Life

Self Cite

View full text Add to dashboard Cite

Lysine-specific methyltransferase 7 (KMT7) SET7/9, aka Set7, Set9, or SetD7, or KMT5 was discovered 20 years ago, yet its biological role remains rather enigmatic. In this review, we analyze the particularities of SET7/9 enzymatic activity and substrate specificity with respect to its biological importance, mostly focusing on its two well-characterized biological functions: cellular proliferation and stress response.

show abstract

KMT Set7/9 is a new regulator of Sam68 STAR-protein

Cited by 16 publications

References 26 publications

p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells

p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells

A Systematic Review to Define the Multi-Faceted Role of Lysine Methyltransferase SETD7 in Cancer

The Role of Lysine Methyltransferase SET7/9 in Proliferation and Cell Stress Response

Contact Info

Product

Resources

About