Medicine and Health Sciences Commons^™

Ier5, A Dna Damage Response Gene, Is Required For Notch-Mediated Induction Of Squamous Cell Differentiation, Li Pan, Madeleine E Lemieux, Tom Thomas, Julia M Rogers, Colin H Lipper, Winston Lee, Carl Johnson, Lynette M Sholl, Andrew P. South, Jarrod A Marto, Guillaume O Adelmant, Stephen C Blacklow, Jon C Aster

Department of Dermatology and Cutaneous Biology Faculty Papers

Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, including IER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes. IER5 is epistatic to PPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage …

Characteristics Of Nontuberculous Mycobacterial Infections At A Midwestern Tertiary Hospital: A Retrospective Study Of 365 Patients., Claire E Hannah, Bradley A Ford, Jina Chung, Dilek Ince, Karolyn A Wanat

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease.

Methods: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, …

Global Mapping Of Transcription Factor Motifs In Human Aging., David Alfego, Ulrich Rodeck, Andres Kriete

Department of Dermatology and Cutaneous Biology Faculty Papers

Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established …

Clinical Phenotypes And Abcc6 Gene Mutations In Brazilian Families With Pseudoxanthoma Elasticum., Caroline Silvério Faria, Qiaoli Li, Haitao Guo, Jouni Uitto, Sylvia Satomi Takeno, Marilia De Arruda Cardoso Smith, Dertia Villalba Freire-Maia

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE; OMIM 264800) manifests with characteristic skin lesions of yellowish papules which coalesce into plaques of inelastic and leathery skin on the predilection sites (1). The ocular findings consist of angioid streaks, choroidal neovascularization and subretinal hemorrhages resulting in loss of visual acuity and occasional blindness. Cardiovascular problems include hypertension, intermittent claudication, and occasional myocardial infarcts and stroke. The prevalence of PXE is estimated to be in the range of 1:50,000-70,000 and to be more frequent in females than in males. The diagnosis can be challenging to clinicians due to late-onset of clinical manifestations and considerable heterogeneity. PXE …

Ubinuclein, A Novel Nuclear Protein Interacting With Cellular And Viral Transcription Factors., S Aho, M Buisson, T Pajunen, Y W Ryoo, J F Giot, H Gruffat, A Sergeant, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

The major target tissues for Epstein-Barr virus (EBV) infection are B lymphocytes and epithelial cells of the oropharyngeal zone. The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection. Here, we characterize a novel cellular protein interacting with the basic domains of EB1 and c-Jun, and competing of their binding to the AP1 consensus site. The transcript is present in a wide variety of human adult, fetal, and tumor tissues, and the protein is …