We showed previously that ICP27 undergoes a head-to-tail intramolecular interaction, and here we show that the cellular mRNA export receptor protein TAP/NXF1 interacts with ICP27 after its head-to-tail association. Several proteins that interact with ICP27 require that the N and C termini of ICP27 be intact. These results demonstrate that the head-to-tail interaction of ICP27 may regulate some of its protein interactions perhaps through alternating between open and closed configurations.”
“Background:

Mutations in the IGF-I receptor (IGF1R) gene can be responsible for intrauterine and postnatal growth disorders.\n\nObjective: Here we report on a novel mutation in the IGF1R gene in a female patient. The aim of our study was to analyze the functional impact of this mutation.\n\nPatient: At birth, the girl’s length was 47 cm [-1.82 SD score (SDS)], and her weight was 2250 C59 Wnt g (-2.26 SDS). Clinical examination revealed microcephaly and retarded cognitive development. She showed no postnatal catch-up growth but had relatively high IGF-I levels (+1.83 to +2.17 SDS).\n\nResults: Denaturing HPLC screening and direct DNA sequencing disclosed a heterozygous missense mutation resulting

in an amino Y-27632 cell line acid exchange from valine to glutamic acid at position 599 (V599E-IGF1R). Using various cell systems, we found that the V599E-IGF1R mutant was not tyrosine phosphorylated and had an impaired downstream signaling in the presence of IGF-I. Flow cytometry and live cell confocal laser scanning microscopy revealed a lack of cell surface expression due to an extensive retention of V599E-IGF1R proteins within the endoplasmic reticulum.\n\nConclusion: The V599E-IGF1R mutation interferes selleck screening library with the receptor’s trafficking path, thereby abrogating proreceptor processing and plasma membrane localization. Diminished cell surface receptor density solely expressed from the

patient’s wild-type allele is supposed to lead to insufficient IGF-I signaling. We hypothesize that this mechanism results in intrauterine and postnatal growth retardation of the affected patient. The reported retention of the nascent IGF1R in the endoplasmic reticulum presents a novel mechanism of IGF-I resistance. (J Clin Endocrinol Metab 95: 2316-2324, 2010)”
“Purpose: The Spanish Urological Club for Oncological Treatment recently developed a scoring model to stratify the recurrence risk in patients treated with intravesical bacillus Calmette-Guerin using gender, age, grade, tumor status, T category, multiplicity and associated carcinoma in situ. We investigated the ability of this model to stratify the recurrence risk in patients with nonmuscle invasive bladder cancer undergoing combination bacillus Calmette-Guerin plus interferon alpha-2B therapy.