The potential use of protein kinase D inhibitors for prevention/treatment of epidermal tumors

Arun, Senthil Nathan; Xie, Dongdong; Dodd, Mary; Zhong, Xiaofeng; Bollag, Wendy B.

doi:10.1016/j.jdermsci.2010.07.015

Cited by 12 publications

(12 citation statements)

References 36 publications

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“…These results confirm that PKD1 is an anti-differentiative and pro-proliferative signaling enzyme in mouse keratinocytes, similar to human keratinocytes [24], but are unique in that they were obtained with the use of the floxed PKD1 mouse model rather than overexpression [40] or RNA interference [24], with the attendant caveats of these methods. Thus, in this study, we used PKD1-floxed mice that possess loxP sites flanking exons 12 through 14 of the PKD1 gene, which encodes part of the catalytic domain.…”

Section: Discussionsupporting

confidence: 69%

Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes

Choudhary

Olala

Kaddour‐Djebbar

et al. 2014

Journal of Dermatological Science

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Background Protein kinase D (PKD or PKD1) is a serine/threonine protein kinase that has been shown to play a role in a variety of cellular processes; however, the function of PKD1 in the skin has not been fully investigated. The balance between proliferation and differentiation processes in the predominant cells of the epidermis, the keratinocytes, is essential for normal skin function. Objective To investigate the effect of PKD1 deficiency on proliferation and differentiation of epidermal keratinocytes. Methods We utilized a floxed PKD1 mouse model such that infecting epidermal keratinocytes derived from these mice with an adenovirus expressing Cre-recombinase allowed us to determine the effect of PKD1 gene loss in vitro. Proliferation and differentiation were monitored using qRT-PCR, Western blot, transglutaminase activity assays, [3H]thymidine incorporation into DNA and cell cycle analysis. Results A significant decrease in PKD1 mRNA and protein levels was achieved in adenoviral Cre-recombinase-infected cells. Deficiency of PKD1 resulted in significant increases in the mRNA and protein expression of various differentiation markers such as loricrin, involucrin, and keratin 10 either basally and/or upon stimulation of differentiation. PKD1-deficient keratinocytes also showed an increase in transglutaminase expression and activity, indicating an anti-differentiative role of PKD1. Furthermore, the PKD1-deficient keratinocytes exhibited decreased proliferation. However, PKD1 loss had no effect on stem cell marker expression. Conclusions Cre-recombinase-mediated knockdown represents an additional approach demonstrating that PKD1 is an anti-differentiative, pro-proliferative signal in mouse keratinocytes.

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Section: Discussionsupporting

confidence: 69%

Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes

Choudhary

Olala

Kaddour‐Djebbar

et al. 2014

Journal of Dermatological Science

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“…Treatment of keratinocytes with resveratrol induced a dose-dependent increase in transglutaminase activity, while simultaneously inhibiting DNA synthesis, with a half-maximal concentration of 35 μM. Finally, resveratrol and 1, 25(OH) 2 D 3 synergistically increased transglutaminase activity [84]. us, resveratrol inhibits keratinocyte proliferation, while stimulating differentiation.…”

Section: Ratsmentioning

confidence: 87%

“…Lee et al showed that resveratrol increased the expression level and deacetylase activity of SIRT1, resulting in apoptosis [172]. Other studies suggest that resveratrol inhibits DNA synthesis, while increasing transglutaminase activity via inhibition of protein kinase D activity [84]. Moreover, activation of SIRT1 by resveratrol could also increase keratinocyte differentiation [83].…”

Section: Keratinocyte Proliferation and Differentiationmentioning

confidence: 99%

“…us, resveratrol could also accelerate cutaneous wound healing through its well-known ability to stimulate keratinocyte differentiation and lipid production [83,84,161]. Collectively, the resveratrol-induced acceleration of cutaneous wound healing can be attributable to activation of SIRT1 and AMPK signaling, antioxidative stress, and enhanced formation of epidermal permeability barrier.…”

Section: Woundmentioning

confidence: 99%

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Role of Resveratrol in Regulating Cutaneous Functions

Wen

Zhang

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

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“…Our laboratory has also shown that PKD1 co(over)-expression increases the promoter activity for the basal layer marker, keratin 5, and decreases the promoter activity of involucrin, a marker of differentiation [12]. More recently, we found that overexpression of a constitutively active PKD1 construct (in which serines 738 and 742, equivalent to serines 744 and 748 in mouse PKD, are mutated to phosphorylation-mimicking glutamates) increases keratinocyte proliferation and a dominant-negative PKD1 construct (in which serines 738 and 742 are mutated to unphosphorylatable alanines) inhibits growth [13]. Jadali and Ghazizadeh [14] also reported a role for PKD1 in the proliferation observed with reentry of growth-arrested mouse keratinocytes into the cell cycle.…”

mentioning

confidence: 99%

Ultraviolet Activation of PKD: Implications for Skin Cancer

Bollag

2011

Future Oncol.

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The potential use of protein kinase D inhibitors for prevention/treatment of epidermal tumors

Cited by 12 publications

References 36 publications

Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes

Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes

Role of Resveratrol in Regulating Cutaneous Functions

Ultraviolet Activation of PKD: Implications for Skin Cancer

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