The role of telomerase activity in psoriatic skin lesions

Jurišić, Davor; Kirin, I; Rabic, Domagoj; Dojčinović, Bojan; Čoklo, Miran; Zamolo, Gordana

doi:10.1016/j.mehy.2006.09.037

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…For example, it has been shown that telomerase activity is increased in the epidermis after it has been exposed to ultraviolet (UV) light or even poison ivy (14). There is also speculation that telomerase can be increased in the epidermis upon inflammation (76). Thus, telomerase may be activated in the epidermis as it is needed for cell proliferation and repair of damage.…”

Section: Telomerase In Human Skinmentioning

confidence: 99%

The role of telomeres in the ageing of human skin

Buckingham

Klingelhutz

2011

Experimental Dermatology

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Skin is a self-renewing tissue that is required to go through extensive proliferation throughout the lifespan of an organism. Telomere shortening acts as a mitotic clock that prevents aberrant proliferation such as cancer. A consequence of this protection is cellular senescence and ageing. The telomerase enzyme complex maintains telomere length in germline cells and in cancer cells. Telomerase is also active in certain somatic cells such as those in the epidermis but is almost undetectable in the dermis. Increasing evidence indicates that telomerase plays a significant role in maintenance of skin function and proliferation. Mutations in telomerase component genes in the disease dyskeratosis congenita result in numerous epidermal abnormalities. Studies also indicate that telomerase activity in epidermal stem cells might have roles that go beyond telomere elongation. Telomeres in skin cells may be particularly susceptible to accelerated shortening because of both proliferation and DNA-damaging agents such as reactive oxygen species. Skin might present an accessible tissue for manipulation of telomerase activity and telomere length with the potential of ameliorating skin diseases associated with ageing.

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Section: Telomerase In Human Skinmentioning

confidence: 99%

The role of telomeres in the ageing of human skin

Buckingham

Klingelhutz

2011

Experimental Dermatology

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“…High activity of telomerase has been implicated in maintaining telomere stability, genome integrity, cell activity, potential long-term proliferative ability and other aspects in cancer cells [ 4 , 5 ]. Telomerase activity is usually low or under detection in normal human cells except human embryonic stem cells and germ cells, but it is highly activated in the immortalized cells and more than 85% of tumor cells during malignant transformation [ 6 - 12 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional coactivator CBP upregulates hTERT expression and tumor growth and predicts poor prognosis in human lung cancers

Guo

Dai

et al. 2014

Oncotarget

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Upregulated expression and activation of human telomerase reverse transcriptase (hTERT) is a hallmarker of lung tumorigenesis. However, the mechanism underlying the aberrant hTERT activity in lung cancer cells remains poorly understood. In this study, we found the transcriptional co-activator CBP as a new hTERT promoter-binding protein that regulated hTERT expression and tumor growth in lung adenocarcinoma cells using a biotin-streptavidin-bead pulldown technique. Chromatin immunoprecipitation assay verified the immortalized cell and tumor cell-specific binding of CBP on hTERT promoter. Overexpression of exogenous CBP upregulated the expression of the hTERT promoter-driven luciferase and endogenous hTERT protein in lung cancer cells. Conversely, inhibition of CBP by CBP-specific siRNA or its chemical inhibitor repressed the expression of hTERT promoter-driven luciferase and endogenous hTERT protein as well as telomerase activity. Moreover, inhibition of CBP expression or activity also significantly reduced the proliferation of lung cancer cells in vitro and tumor growth in an xenograft mouse model in vivo. Immunohistochemical analysis of tissue microarrays of lung cancers revealed a positive correlation between CBP and hTERT. Importantly, the patients with high CBP and hTERT expression had a significantly shorter overall survival. Furthermore, CBP was found to interact with and acetylate transactivator Sp1 in lung cancer cells. Inhibition of CBP by CBP-specific siRNA or its chemical inhibitor significantly inhibited Sp1 acetylation and its binding to the hTERT promoter. Collectively, our results indicate that CBP contributes to the upregulation of hTERT expression and tumor growth, and overexpression of CBP predicts poor prognosis in human lung cancers.

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“…Putative roles for primary keratinocyte defects in psoriasis include the corneodesmosin gene (Capon et al, 2004) and abnormal expression of amphiregulin (Chung et al, 2005) and telomerase (Jurisic et al, 2007) by keratinocytes. Neurogenic pathways may also be important in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of the Orphan Nuclear Receptor NURR1 in Psoriasis and Modulation following TNF-α Inhibition

O'Kane

Markham

McEvoy

et al. 2008

Journal of Investigative Dermatology

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The orphan nuclear receptor NURR1 belongs to the NR4A subfamily of transcription factors which are emerging as important mediators of cytokine and growth factor signaling. The transcriptional function of these ligand-independent and constitutively active receptors is controlled at the level of expression and nuclear localization. This study examines the expression of NURR1 in psoriasis and biological effects on this receptor following inhibition of tumor necrosis factor-alpha (TNF-alpha) signaling. We report increased expression of NURR1 mRNA and protein in involved psoriasis skin compared with uninvolved and normal skin, which correlates significantly (P=0.0055) with clinical measures of the psoriasis area and severity index. Enhanced NURR1 expression localizes to both nucleus and cytoplasm of cells of involved epidermis, blood vessels, and inflammatory infiltrates, in contrast to predominant cytoplasmic distribution in uninvolved and normal skin. Endogenous NURR1 levels are rapidly and selectively increased in response to proinflammatory agonists and growth factors in normal dermal endothelial cells. Following TNF-alpha inhibition with infliximab or etanercept, NURR1 mRNA and protein levels in involved skin are significantly decreased and cytoplasmic distribution is restored. These findings establish the aberrant expression and distribution of NURR1 in psoriasis and suggest that clinical benefits of TNF-alpha inhibition may be mediated through altered NURR1 activity.

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The role of telomerase activity in psoriatic skin lesions

Cited by 5 publications

References 10 publications

The role of telomeres in the ageing of human skin

The role of telomeres in the ageing of human skin

Transcriptional coactivator CBP upregulates hTERT expression and tumor growth and predicts poor prognosis in human lung cancers

Increased Expression of the Orphan Nuclear Receptor NURR1 in Psoriasis and Modulation following TNF-α Inhibition

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