Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1.

Interferon induced transmembrane proteins (IFITMs) play a dual role in the restriction of RNA viruses and in cancer progression, yet the mechanism of their action remains unknown. Currently, there is no data about the basic biochemical features or biophysical properties of the IFITM1 protein. In this work, we report on description and biochemical characterization of three conformational variants/oligomeric species of recombinant IFITM1 protein derived from an expression system.

DNA Demethylation Switches Oncogenic ΔNp63 to Tumor Suppressive TAp63 in Squamous Cell Carcinoma.

The gene encodes two major protein variants; TAp63 contains a p53-like transcription domain and consequently has tumor suppressor activities whereas ΔNp63 lacks this domain and acts as an oncogene. The two variants show distinct expression patterns in normal tissues and tumors, with lymphocytes and lymphomas/leukemias expressing TAp63, and basal epithelial cells and some carcinomas expressing high levels of ΔNp63, most notably squamous cell carcinomas (SCC). Whilst the transcriptional functions of TAp63 and ΔNp63 isoforms are known, the mechanisms involved in their regulation are poorly understood.

Cryptic in vitro ubiquitin ligase activity of HDMX towards p53 is probably regulated by an induced fit mechanism.

HDMX and its homologue HDM2 are two essential proteins for the cell; after genotoxic stress, both are phosphorylated near to their RING domain, specifically at serine 403 and 395, respectively. Once phosphorylated, both can bind the p53 mRNA and enhance its translation; however, both recognize p53 protein and provoke its degradation under normal conditions. HDM2 has been well-recognized as an E3 ubiquitin ligase, whereas it has been reported that even with the high similarity between the RING domains of the two homologs, HDMX does not have the E3 ligase activity.

The foggy world(s) of p63 isoform regulation in normal cells and cancer.

The p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways.

Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue.

Human keratin 36 (K36) is a member of the hair keratin family and is a marker of hair cortex differentiation. The human gene is located on the long arm of chromosome 17 and belongs to the cluster of structurally unrelated acidic hair keratins. Recently, it has been reported that mRNA is specifically expressed in normal tongue epithelium and downregulated in squamous cell carcinomas of the mobile tongue.

Oncogenic Viral Protein Interactions with p53 Family Proteins.

Background: Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor.

[Application of PLA Method for Detection of p53/p63/p73 Complexes in Situ in Tumour Cells and Tumour Tissue].

Background: PLA (proximity ligation assay) can be used for detection of protein-protein interactions in situ directly in cells and tissues. Due to its high sensitivity and specificity it is useful for detection, localization and quantification of protein complexes with single molecule resolution. One of the mechanisms of mutated p53 gain of function is formation of proten-protein complexes with other members of p53 family - p63 and p73.

ΔNp63α expression induces loss of cell adhesion in triple-negative breast cancer cells.

Background: p63, a member of the p53 protein family, plays key roles in epithelial development and carcinogenesis. In breast cancer, p63 expression has been found predominantly in basal-A (epithelial-type) triple-negative breast carcinomas (TNBC). To investigate the functional role of p63 in basal-A TNBC, we created MDA-MB-468 cell lines with inducible expression of the two major N-terminal p63 isoforms, TAp63α and ∆Np63α.

Pain and emotional processing in psychological trauma.

Extreme psychological and physical traumas cause dramatic symptom patterns which are insufficiently described by the psychiatric diagnostic criteria of post traumatic stress disorders (PTSD). Additionally, due to the neurobiological proximity and similarity of processing mechanisms of physical and psychological pain stimulation and extremely negative emotions, the patients often suffer from persistent pains even after the somatic healing process is completed. Epidemiological studies confirm the joint occurrence of pain and PTSD.

[Illness behavior and expectations on physician-patient relationships of medical students in the second and fifth year of education].

We investigated illness behaviour and treatment expectations of future physicians. 209 medical students in their second and 110 students in their fifth year of education were examined by means of a specific questionnaire and the Biographic Inventory for Diagnosis of Abnormal Behaviour (BIV). As to our questionnaire we found a six factors solution that could explain 44% of the variance.

[Interdisciplinary longitudinal curriculum "Medical Psychology, Psychotherapy and Psychosomatics." Experiences from the preclinical segment].

The departments of Medical Psychology, Psychosomatics and Psychotherapy developed an interdisciplinary longitudinal curriculum in order to coach medical students for the whole length of their medical education. Experiences from the first four undergraduate semesters are reported. 46 students (33 females, 13 males), mean age 22.

Teaching psychosomatic medicine: predictors of students' attitudes toward a compulsory course.

One hundred five medical students (59 males, 46 females, mean age 25.7 +/- 2.5 years) were asked to evaluate a one-semester course in psychosomatic medicine.

[Pain intensity, mood and pain-alleviating actions in pre-chronic low back pain patients].

Introduction: The present study examines the correlations between pain intensity, mood and pain-alleviating actions in pre-chronic low back pain patients. The three variables were obtained with the Ulm Pain Diary (Ulmer Schmerztagebuch, UST).

Methods: Thirty-eight patients with low back pain described pain intensity, effect of pain on mood and medication as well as other therapies over a 3-week period (21 days).