Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling

Molecular switches are essential modules in signaling networksand transcriptional reprogramming. Here, we describe a role forsmall ubiquitin-related modifier SUMO as a molecular switch inepidermal growth factor receptor (EGFR) signaling. Using quantita-tive mass spectrometry, we compare the endogenous SUMOproteomes of HeLa cells before and after EGF stimulation. Thereby,we identify a small group of transcriptional coregulators includingIRF2BP1, IRF2BP2, and IRF2BPL as novel players in EGFR signaling.Comparison of cells expressing wild type or SUMOylation-deficientIRF2BP1indicates that transient deSUMOylation of IRF2BP proteinsis important for appropriate expression of immediate early genesincludingdual specificity phosphatase1(DUSP1, MKP-1) and thetranscription factor ATF3. We find that IRF2BP1is a repressor,whose transient deSUMOylation on the DUSP1promoter allows—and whose timely reSUMOylation restricts—DUSP1transcription.Our work thus provides a paradigm how comparative SUMOproteome analyses serve to reveal novel regulators in signal trans-duction and transcription

Apical root resorption six and 12 months after initiation of fixed orthodontic appliance therapy

Contains fulltext : 48027.pdf (publisher's version ) (Open Access

Identification of orthodontic patients at risk of severe apical root resorption.

Contains fulltext : 80408.pdf (publisher's version ) (Closed access)INTRODUCTION: Current information suggests that the major variation in orthodontic root resorption can be explained by differences in individual predisposition. Our aim was therefore to test the predictive value of the amount of maxillary incisor resorption about 6 and 12 months after bracket placement for the resorption at appliance removal. METHODS: We measured tooth length of the maxillary incisors on digitally converted periapical radiographs, adjusted for projection errors, made before treatment (T1), about 6 months (T2) and 12 months (T3) after bracket placement, and at the end of active treatment (T4) of 267 prospectively enrolled orthodontic patients, and interpreted reduced tooth length as apical root resorption. Anatomic and occlusal parameters were scored on the T1 radiographs and study models. Anamnestic and treatment parameters were collected from standardized recordings in the charts. RESULTS: The Spearman R for resorption of each incisor ranged from 0.61 to 0.76 at T2 vs T4, and from 0.77 to 0.88 at T3 vs T4 (P 1.0 mm of resorption at T2 and 0.5% of those with no incisors with >2.0 mm of resorption at T3 had at least 1 incisor with >5.0 mm of resorption at T4. Amount of resorption at T3 and maxillary tooth extraction were included in the final prediction model for resorption of the most severely affected central and lateral incisors at T4, with explained variances of 0.71 and 0.67, respectively. Treatment duration and time with square wires was not related to resorption (P >0.05). CONCLUSIONS: Patients at risk of severe apical root resorption can be identified according to the amount of resorption during the initial treatment stages

Apical root resorption 6 months after initiation of fixed orthodontic appliance therapy.

Contains fulltext : 48020.pdf (publisher's version ) (Closed access)INTRODUCTION: Individual predisposition might be a major reason for the observed variation in apical orthodontic root resorption. If so, resorption might be expressed during the initial stages of orthodontic therapy in patients at risk. METHODS: To explore this hypothesis, we evaluated standardized, digitized periapical radiographs made before treatment (T1) and at a mean period of 6.4 months (SD 0.9) after placement of maxillary incisor brackets (T2) in 290 patients (age range, 10.1 to 57.1 years at T1). Anamnestic and treatment parameters were recorded according to a protocol, and maxillary incisor irregularity was measured on T1 study models. RESULTS: The mean average root resorption for 4 incisors was 0.53 mm (SD 0.47), whereas the sample mean of the most severely resorbed tooth per patient was 1.18 mm (SD 0.86). A total of 4.1% of the patients had an average resorption of 1.5 mm or more, and 15.5% had at least 1 tooth with 2.0 mm or more resorption. The maximum amount of resorption was 4.4 mm. Multivariate linear regression showed that deviated root form and increased T1-to-T2 time period were risk factors for apical root resorption of the central incisors; normal root form and wide roots were preventive factors, with an explained variance of 14%. Similarly, long roots, narrow roots, and increased T1-to-T2 time period were risk factors for resorption of the lateral incisors, whereas normal root form was a preventive factor, with an explained variance of 24%. Parameters associated with use of rectangular wire, presence of incisor irregularity, and history of trauma were not identified as risk factors. Use of elastics was not included in the regression analyses. CONCLUSIONS: Root resorption can begin in the early leveling stages of orthodontic treatment. About 4.1% of patients studied had an average resorption of 1.5 mm or more of the 4 maxillary incisors, and about 15.5% had 1 or more maxillary incisors with resorption of 2.0 mm or more from 3 to 9 months after initiation of fixed appliance therapy. Although teeth with long, narrow, and deviated roots are at increased risk of resorption during this early stage, the explained variance of these risk factors is less than 25%