scholarly journals The PDZ-Binding Motif of HPV16-E6 Oncoprotein Modulates the Keratinization and Stemness Transcriptional ProfileIn Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Enoc Mariano Cortés-Malagón ◽  
Carmen Palacios-Reyes ◽  
Sandra Romero-Cordoba ◽  
Daniel Mendoza-Villanueva ◽  
Jaime Escobar-Herrera ◽  
...  

Objective. The aim of this work was to compare the early gene expression profiles in the skin of HPV16-E6 transgenic mice regulated by the E6 PDZ-binding motif.Materials and Methods.The global transcriptional profiles in dorsal skin biopsies from K14E6 and K14E6Δ146-151 transgenic mice were compared using microarrays. Relevant genes obtained from the most differentially expressed processes were further examined by RT-qPCR, in situ RT-PCR, Western blot, or immunofluorescence.Results.The transcriptomic landscape of K14E6 versus K14E6Δ146-151 shows that the most affected expression profiles were those related to keratinocyte differentiation, stem cell maintenance, and keratinization. Additionally, downregulation of epidermal stemness markers such as K15 and CD34, as well as the upregulation of cytokeratin 6b, appeared to be dependent on the E6 PDZ-binding motif. Finally, wound healing, a physiological process linked to stemness, is impaired in the K14E6 mice compared to K14E6Δ146-151.Conclusion.The E6 PDZ-binding motif appears to affect stemness and keratinization during early stages of skin carcinogenesis. As E6 plays a significant role in HPV-induced skin carcinogenesis, the K14E6 versus K14E6Δ146-151 transcriptional profile provides a source of valuable data to uncover novel E6 functions in the skin.

Agronomy ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1312
Author(s):  
Jia Liu ◽  
Weicong Qi ◽  
Haiying Lu ◽  
Hongbo Shao ◽  
Dayong Zhang

Salt tolerance is an important trait in soybean cultivation and breeding. Plant responses to salt stress include physiological and biochemical changes that affect the movement of water across the plasma membrane. Plasma membrane intrinsic proteins (PIPs) localize to the plasma membrane and regulate the water and solutes flow. In this study, quantitative real-time PCR and yeast two-hybridization were engaged to analyze the early gene expression profiles and interactions of a set of soybean PIPs (GmPIPs) in response to salt stress. A total of 20 GmPIPs-encoding genes had varied expression profiles after salt stress. Among them, 13 genes exhibited a downregulated expression pattern, including GmPIP1;6, the constitutive overexpression of which could improve soybean salt tolerance, and its close homologs GmPIP1;7 and 1;5. Three genes showed upregulated patterns, including the GmPIP1;6 close homolog GmPIP1;4, when four genes with earlier increased and then decreased expression patterns. GmPIP1;5 and GmPIP1;6 could both physically interact strongly with GmPIP2;2, GmPIP2;4, GmPIP2;6, GmPIP2;8, GmPIP2;9, GmPIP2;11, and GmPIP2;13. Definite interactions between GmPIP1;6 and GmPIP1;7 were detected and GmPIP2;9 performed homo-interaction. The interactions of GmPIP1;5 with GmPIP2;11 and 2;13, GmPIP1;6 with GmPIP2;9, 2;11 and GmPIP2;13, and GmPIP2;9 with itself were strengthened upon salt stress rather than osmotic stress. Taken together, we inferred that GmPIP1 type and GmPIP2 type could associate with each other to synergistically function in the plant cell; a salt-stress environment could promote part of their interactions. This result provided new clues to further understand the soybean PIP–isoform interactions, which lead to potentially functional homo- and heterotetramers for salt tolerance.


2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Purnima Gupta ◽  
Naveed Shahzad ◽  
Alexis Harold ◽  
Masahiro Shuda ◽  
Assunta Venuti ◽  
...  

ABSTRACT Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, viral oncogenes required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analyzed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV. In particular, the MCPyV early gene downregulated the expression of the tumor suppressor gene N-myc downstream-regulated gene 1 (NDRG1) in MCPyV gene-expressing NIKs and hTERT-MCPyV gene-expressing human keratinocytes (HK) compared to their expression in the controls. In MCPyV-positive MCC cells, the expression of NDRG1 was downregulated by the MCPyV early gene, as T antigen knockdown rescued the level of NDRG1. In addition, NDRG1 overexpression in hTERT-MCPyV gene-expressing HK or MCC cells resulted in a decrease in the number of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV gene-expressing HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of the cyclin-dependent kinase 2 (CDK2) and cyclin D1 proteins. Overall, NDRG1 plays an important role in MCPyV-induced cellular proliferation. IMPORTANCE Merkel cell carcinoma was first described in 1972 as a neuroendocrine tumor of skin, most cases of which were reported in 2008 to be caused by a PyV named Merkel cell polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus-induced carcinogenesis. However, it is still a new field, and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV, as opposed to other PyVs, in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies, thereby providing hope for the management of patients suffering from this highly aggressive cancer.


2018 ◽  
Vol 108 (5) ◽  
pp. 627-640 ◽  
Author(s):  
Peri A. Tobias ◽  
David I. Guest ◽  
Carsten Külheim ◽  
Robert F. Park

Austropuccinia psidii, causal agent of myrtle rust, was discovered in Australia in 2010 and has since become established on a wide range of species within the family Myrtaceae. Syzygium luehmannii, endemic to Australia, is an increasingly valuable berry crop. Plants were screened for responses to A. psidii inoculation, and specific resistance, in the form of localized necrosis, was determined in 29% of individuals. To understand the molecular basis underlying this response, mRNA was sequenced from leaf samples taken preinoculation, and at 24 and 48 h postinoculation, from four resistant and four susceptible plants. Analyses, based on de novo transcriptome assemblies for all plants, identified significant expression changes in resistant plants (438 transcripts) 48 h after pathogen exposure compared with susceptible plants (three transcripts). Most significantly up-regulated in resistant plants were gene homologs for transcription factors, receptor-like kinases, and enzymes involved in secondary metabolite pathways. A putative G-type lectin receptor-like kinase was exclusively expressed in resistant individuals and two transcripts incorporating toll/interleukin-1, nucleotide binding site, and leucine-rich repeat domains were up-regulated in resistant plants. The results of this study provide the first early gene expression profiles for a plant of the family Myrtaceae in response to the myrtle rust pathogen.


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