C/EBPα regulates CRL4<sup>Cdt2</sup>-mediated degradation of p21 in response to UVB-induced DNA damage to control the G<sub>1</sub>/S checkpoint

Hall, Jonathan; Bereman, Michael S.; Nepomuceno, Angelito I.; Thompson, Elizabeth A.; Muddiman, David C.; Smart, Robert C.

doi:10.4161/15384101.2014.962957

Cited by 20 publications

(16 citation statements)

References 54 publications

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“…UV can be divided into UVA, UVB, and UVC according to the spectrum. Among them, UVB is closely correlated with epidermal cell photodamage, leading to sunburn, photoaging, DNA damage, and photocarcinogenesis [90–92]. Keratinocytes are the major target of UVB-induced skin damage because they serve as the predominant component in the epidermal structure.…”

Section: Discussionmentioning

confidence: 99%

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

et al. 2017

Oxidative Medicine and Cellular Longevity

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The mechanistic target of Rapamycin (MTOR) protein is a crucial signaling regulator in mammalian cells that is extensively involved in cellular biology. The function of MTOR signaling in keratinocytes remains unclear. In this study, we detected the MTOR signaling and autophagy response in the human keratinocyte cell line HaCaT and human epidermal keratinocytes treated with MTOR inhibitors. Moreover, we detected the impact of MTOR inhibitors on keratinocytes exposed to the common carcinogenic stressors ultraviolet B (UVB) and UVA radiation. As a result, keratinocytes were sensitive to the MTOR inhibitors Rapamycin, everolimus, Torin 1, and pp242, but the regulation of MTOR downstream signaling was distinct. Next, autophagy induction only was observed in HaCaT cells treated with Rapamycin. Furthermore, we found that MTOR signaling was insensitive to UVB but sensitive to UVA radiation. UVB treatment also had no impact on the inhibition of MTOR signaling by MTOR inhibitors. Finally, MTOR inhibition by Rapamycin, everolimus, or pp242 did not affect the series of biological events in keratinocytes exposed to UVB, including the downregulation of BiP and PERK, activation of Histone H2A and JNK, and cleavage of caspase-3 and PARP. Our study demonstrated that MTOR inhibition in keratinocytes cannot always induce autophagy, and the MTOR pathway does not play a central role in the UVB triggered cellular response.

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Section: Discussionmentioning

confidence: 99%

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…The expression of C/EBPα in immature myeloid cells can block the cell cycle at G1/S, preventing cells from differentiation eventually. The differentiation from myeloid progenitors to granulocyte‐macrophage progenitors will be abnormal if lacking C/EBPα . C/EBPβ promotes myeloid progenitors differentiate into functional MDSCs.…”

Section: Main Functional Characteristics Of Mdscsmentioning

confidence: 99%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid-derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side-effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.

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“…Moreover, DCAFs have been found to recognise various substrates that play critical roles in different biological processes such as cell cycle progression (e.g. p21, p27, CHK1, PTEN) , genome stability maintenance (e.g. DDB2, CDT1) and gene expression regulation (e.g.…”

Section: Introductionmentioning

confidence: 99%

Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

Liu

et al. 2019

The Journal of Pathology

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Inflammation is well known as an important driver of the initiation of colitis-associated cancer (CAC). Some cytokines, such as IL-6 and TNF- can activate expression of the oncogene c-Myc (MYC) and regulate its downstream effects. Cullin-RING E3 Ligases (CRLs) are emerging as master regulators controlling tumorigenesis.Here, we demonstrate that two cullin genes, CUL4A and CUL4B, but not other members, are specifically overexpressed in CAC tumour samples and positively correlate with levels of the proinflammatory cytokines IL-1 and IL-6. In vitro experiments revealed that the transcription factor c-Myc can specifically activate the expression of CUL4A and CUL4B by binding to a conserved site (CACGTG) located in their promoters. Additionally, we found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4 DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7). Overexpression of c-Myc in human colon epithelial cells resulted in the accumulation of CUL4A, CUL4B and DCAF4, but degradation of ST7. In contrast, knockdown of c-Myc, CUL4A or CUL4B in the colon adenocarcinoma cell line HT29 caused accumulation of ST7 and inhibition of cell proliferation, colony formation ability and in vivo tumour growth. Collectively, our results provide in vitro and in vivo evidence that c-Myc regulates CRL4 DCAF4 E3 ligase activity to mediate ubiquitination of ST7, whose presence is physiologically essential for CAC tumorigenesis.No conflicts of interest were declared. ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) [16,17]. The human genome encodes two E1s, ∼40 E2s and more than 600 E3s [18,19]. Of these E3 ligases, Cullin-RING

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C/EBPα regulates CRL4^Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G₁/S checkpoint

Cited by 20 publications

References 54 publications

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

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C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

Cited by 20 publications

References 54 publications

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Inflammation‐dependent overexpression of c‐Myc enhances CRL4DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer

Contact Info

Product

Resources

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C/EBPα regulates CRL4^Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G₁/S checkpoint

Inflammation‐dependent overexpression of c‐Myc enhances CRL4^DCAF4 E3 ligase activity and promotes ubiquitination of ST7 in colitis‐associated cancer