Transcriptome analysis of the circadian clock gene BMAL1 deletion with opposite carcinogenic effects

Emisoglu-Kulahli, Handan; Gül, Şeref; Morgil, Hande; Ozcan, Onur; Aygenli, Fatih; Selvi, Saba; Kavaklı, İbrahim Halil; Öztürk, Nuri

doi:10.1007/s10142-020-00757-6

Cited by 12 publications

(8 citation statements)

References 53 publications

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“…Only experimentally determined PPI data having a confidence score of 0.4 or higher in the STRING database was allowed to include and a maximum of 50 interactors per protein in the first shell was allowed to construct networks 36,37 . Networks were analyzed as explained before 11 . In short, Cytoscape 3.6.0 was used to visualize and calculate the properties of PPI networks.…”

Section: Methodsmentioning

confidence: 99%

“…U2OS-BioID2 or U2OS-PER2-BioID2 cells were seeded on 60 mm dishes as described previously. 11 Briefly, after harvesting the cells, mRNAs were isolated using NucleoSpin RNA Purification Kit (Macherey Nagel, Germany, cat no: REF 740962) and converted to cDNA using ProtoScript First Strand cDNA Synthesis kit (NEB, Ipswich, MA, cat no: E6300S) with oligo dT option. Finally, cDNAs were subjected to SYBR Green-based RT-qPCR assay using Maxima SYBR Green/ROX qPCR Master Mix (Thermo Fischer Scientific, Cat no: K0222).…”

Section: Mrna Analysis With Qpcrmentioning

confidence: 99%

“…It has been shown that the circadian clock regulates 10% of the transcriptome and 20%–40% of the proteome 10 . With the addition of recent gene‐editing technologies, the method of high‐throughput screening of transcriptional targets continues to reveal a more precise model of the circadian function of the core clock proteins and novel modulators for the circadian relevant responses 11 . In addition, genetics, computational and biochemical methods have also suggested that there are likely more core clock or clock‐modifying genes 12–16 .…”

Section: Introductionmentioning

confidence: 99%

“…10 With the addition of recent gene-editing technologies, the method of highthroughput screening of transcriptional targets continues to reveal a more precise model of the circadian function of the core clock proteins and novel modulators for the circadian relevant responses. 11 In addition, genetics, computational and biochemical methods have also suggested that there are likely more core clock or clock-modifying genes. [12][13][14][15][16] Moreover, post-translational stability and modifications are actively regulated by the circadian clock.…”

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confidence: 99%

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Proteome analysis of the circadian clock protein PERIOD2

et al. 2022

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Circadian rhythms are a series of endogenous autonomous 24‐h oscillations generated by the circadian clock. At the molecular level, the circadian clock is based on a transcription–translation feedback loop, in which BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME (CRY) and PERIOD (PER) genes of the negative arm as well as the circadian clock‐regulated genes. There are three PER proteins, of which PER2 shows the strongest oscillation at both stability and cellular localization level. Protein–protein interactions (PPIs) or interactome of the circadian clock proteins have been investigated using classical methods such as two‐dimensional gel electrophoresis, immunoprecipitation‐coupled mass spectrometry, and yeast‐two hybrid assay where the dynamic and weak interactions are difficult to catch. To identify the interactome of PER2 we have adopted proximity‐dependent labeling with biotin and mass spectrometry‐based identification of labeled proteins (BioID). In addition to known interactions with such as CRY1 and CRY2, we have identified several new PPIs for PER2 and confirmed some of them using co‐immunoprecipitation technique. This study characterizes the PER2 protein interactions in depth, and it also implies that using a fast BioID method with miniTurbo or TurboID coupled to other major circadian clock proteins might uncover other interactors in the clock that have yet to be discovered.

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Section: Methodsmentioning

confidence: 99%

Section: Mrna Analysis With Qpcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Proteome analysis of the circadian clock protein PERIOD2

et al. 2022

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“…The lentivirus preparation, transduction of U2OS cells and selection of the knockout candidates with puromycin (at 0.5 mg/mL concentration) were performed following a previously published protocol 60,61 . Cell lysates of the knockout candidates were analyzed for CRY1, CRY2 and Actin by immunoblotting using the following antibodies: anti-CRY1 (A302-614A, Bethyl Labs Inc. Montgomery, TX., USA), anti-CRY2 (A302-615A, Bethyl Labs), and anti-Actin (CST-4967S, Cell Signaling Technology, Boston, MA, USA).…”

Section: Generation Of Cry1 Knockout U2os Cell Linementioning

confidence: 99%

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Gül

Akyel

Gul

et al. 2021

Preprint

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Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous level of the CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis is unknown. Here, we discovered a molecule that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The small molecule, called M47, selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and the period of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 enhanced degradation rate of the CRY1 level in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Finally, systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the p53 mutation.

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Redox and metabolic reprogramming in breast cancer and cancer‐associated adipose tissue

Zakic,

Pekovic‐Vaughan,

Cvoro

et al. 2023

FEBS Letters

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Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer‐associated adipose tissue (CAAT). Understanding how the redox‐metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo‐organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell‐specific redox‐metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.

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Transcriptome analysis of the circadian clock gene BMAL1 deletion with opposite carcinogenic effects

Cited by 12 publications

References 53 publications

Proteome analysis of the circadian clock protein PERIOD2

Proteome analysis of the circadian clock protein PERIOD2

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Redox and metabolic reprogramming in breast cancer and cancer‐associated adipose tissue

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