The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Elizabeth A White - One of the best experts on this subject based on the ideXlab platform.
-
ptpn14 degradation by high risk human papillomavirus e7 limits Keratinocyte differentiation and contributes to hpv mediated oncogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Hee Won Kim, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human Keratinocytes but the role of PTPN14 in Keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs Keratinocyte differentiation. Deletion of PTPN14 from primary human Keratinocytes decreased Keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted Keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary Keratinocytes and HPV+ but not HPV- cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs Keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.
-
ptpn14 degradation by high risk human papillomavirus e7 limits Keratinocyte differentiation and contributes to hpv mediated oncogenesis
bioRxiv, 2018Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human Keratinocytes but the role of PTPN14 in Keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate RB1 but cannot degrade PTPN14 we found that high-risk HPV E7-mediated PTPN14 degradation impairs Keratinocyte differentiation. Deletion of PTPN14 from primary human Keratinocytes decreased Keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted Keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary Keratinocytes and HPV-positive but not HPV-negative cancers exhibit a gene expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs Keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.
Yelin Wu - One of the best experts on this subject based on the ideXlab platform.
-
the antimicrobial protein reg3a regulates Keratinocyte proliferation and differentiation after skin injury
Immunity, 2012Co-Authors: Dongqing Li, Katherine A Radek, Yanchun Quan, Changwei Li, Beda Muehleisen, Zhiheng Li, Tian Zhang, Hyun Jeong Park, Ziwei Jiang, Yelin WuAbstract:Summary Epithelial Keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in Keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by Keratinocytes is induced by interleukin-17 (IL-17) via activation of Keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on Keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin Keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.
Joshua Hatterschide - One of the best experts on this subject based on the ideXlab platform.
-
ptpn14 degradation by high risk human papillomavirus e7 limits Keratinocyte differentiation and contributes to hpv mediated oncogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Hee Won Kim, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human Keratinocytes but the role of PTPN14 in Keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs Keratinocyte differentiation. Deletion of PTPN14 from primary human Keratinocytes decreased Keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted Keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary Keratinocytes and HPV+ but not HPV- cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs Keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.
-
ptpn14 degradation by high risk human papillomavirus e7 limits Keratinocyte differentiation and contributes to hpv mediated oncogenesis
bioRxiv, 2018Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human Keratinocytes but the role of PTPN14 in Keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate RB1 but cannot degrade PTPN14 we found that high-risk HPV E7-mediated PTPN14 degradation impairs Keratinocyte differentiation. Deletion of PTPN14 from primary human Keratinocytes decreased Keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted Keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary Keratinocytes and HPV-positive but not HPV-negative cancers exhibit a gene expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs Keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.
Nicole Maasszabowski - One of the best experts on this subject based on the ideXlab platform.
-
the lysosomal cysteine protease cathepsin l regulates Keratinocyte proliferation by control of growth factor recycling
Journal of Cell Science, 2005Co-Authors: Thomas Reinheckel, Nicole Maasszabowski, Sascha Hagemann, Susanne Dollwetmack, Elke Martinez, Tobias Lohmuller, Gordana Zlatkovic, Desmond J Tobin, Christoph PetersAbstract:Mice deficient for cathepsin L (CTSL) show epidermal hyperplasia due to a hyperproliferation of basal Keratinocytes. Here we show that the critical function of CTSL in the skin is Keratinocyte specific. This is revealed by transgenic re-expression of CTSL in the Keratinocytes of ctsl-/- mice, resulting in a rescue of the ctsl-/- skin phenotype. Cultivation of primary mouse Keratinocytes with fibroblast- and Keratinocyte-conditioned media, as well as heterologous organotypic co-cultures of mouse fibroblasts and human Keratinocytes, showed that the altered Keratinocyte proliferation is caused primarily by CTSL-deficiency in Keratinocytes. In the absence of EGF, wild type and CTSL-knockout Keratinocytes proliferate with the same rates, while in presence of EGF, ctsl-/- Keratinocytes showed enhanced proliferation compared with controls. Internalization and degradation of radioactively labeled EGF was identical in both ctsl-/- and ctsl+/+ Keratinocytes. However, ctsl-/- Keratinocytes recycled more EGF to the cell surface, where it is bound to the EGF-receptor, which is also more abundant in ctsl-/- cells. We conclude that the hyperproliferation of Keratinocytes in CTSL-knockout mice is caused by an enhanced recycling of growth factors and growth factor receptors from the endosomes to the Keratinocyte plasma membrane, which result in sustained growth stimulation.
-
Keratinocyte growth regulation in defined organotypic cultures through il 1 induced Keratinocyte growth factor expression in resting fibroblasts
Journal of Investigative Dermatology, 2000Co-Authors: Nicole Maasszabowski, Hansjurgen Stark, Norbert E FusenigAbstract:Balanced Keratinocyte proliferation and differentiation resulting in regular tissue organization strictly depend on dermal support. Organotypic cultures represent biologically relevant in vitro models to study the molecular mechanism of the underlying dermal–epidermal interactions. To mimic the state of resting fibroblasts in the dermis, postmitotic (irradiated) fibroblasts were incorporated in the collagen matrix, where they typically support epidermal proliferation and tissue organization. In coculture with Keratinocytes, fibroblasts exhibit an enhanced expression of Keratinocyte growth factor and the interleukin-1 receptor (type I), which further increase with culture time. In cocultured Keratinocytes, Keratinocyte growth factor receptor as well as RNA expression and protein release of interleukin-1α and interleukin-1β are upregulated. We hypothesized that the modulated cytokine expression represents a basic mechanism for Keratinocyte growth regulation. The functional significance of this double paracrine pathway, i.e., induction of Keratinocyte growth factor expression in fibroblasts by Keratinocytes via release of interleukin-1, was confirmed by interfering with both signaling elements: (i) interleukin-1-neutralizing antibodies and interleukin-1 receptor antagonist significantly inhibited Keratinocyte growth factor release, Keratinocyte proliferation, and tissue formation comparable to the effect produced by Keratinocyte-growth-factor-blocking antibodies; (ii) addition of Keratinocyte growth factor to cocultures with inactivated interleukin-1 pathway completely reverted growth inhibition; (iii) in organotypic cocultures with subthreshold fibroblast numbers both interleukin-1 and Keratinocyte growth factor restored the impaired epidermal morphogenesis. Thus, epidermal tissue regeneration in organotypic cocultures is mainly regulated by Keratinocyte-derived interleukin-1 signaling, which induces Keratinocyte growth factor expression in cocultured fibroblasts. This demonstrates a novel role for interleukin-1 in skin homeostasis substantiating data from wound healing studies in vivo.
Peter J Polverini - One of the best experts on this subject based on the ideXlab platform.
-
aberrant production of interleukin 8 and thrombospondin 1 by psoriatic Keratinocytes mediates angiogenesis
American Journal of Pathology, 1994Co-Authors: Brian J Nickoloff, Raj S Mitra, James Varani, Vishva M Dixit, Peter J PolveriniAbstract:Psoriasis is a common inherited skin disease that is characterized by hyperproliferation of epidermal Keratinocytes and excessive dermal angiogenesis. A growing body of evidence supports a key pathogenetic role for activated Keratinocytes in the angiogenic response that accompanies psoriasis. We investigated the role of psoriatic epidermis in the aberrant expression of angiogenesis by examining the ability of pure populations of multipassaged Keratinocytes obtained from the skin of normal individuals and psoriatic patients to induce angiogenesis in vivo in the rat corneal bioassay and endothelial cell chemotaxis in vitro. Media conditioned by Keratinocytes from psoriatic patients, including both symptomless skin and psoriatic plaques, induced vigorous angiogenic responses in over 90% of corneas tested and potently stimulated directional migration of capillary endothelial cells in vitro. In contrast, conditioned medium from normal Keratinocyte cultures was weakly positive in less than 10% of corneas assayed and failed to stimulate endothelial cell chemotaxis. Furthermore, Keratinocytes from psoriatic skin exhibited a 10- to 20-fold increase in interleukin-8 production and a seven-fold reduction in thrombospondin-1 production. The angiogenic activity present in Keratinocyte-conditioned media from psoriatic patients was suppressed by adding either highly purified thrombospondin-1 (125 ng) or following the addition of either normal Keratinocyte-conditioned media or neutralizing interleukin-8 antibody. We conclude that psoriatic Keratinocytes are phenotypically different from normal Keratinocytes with respect to their angiogenic capacity and that this aberrant phenotype is attributable to a defect in the overproduction of interleukin-8 and a deficiency in the production of the angiogenesis inhibitor thrombospondin-1.
