Women's College, Kolkata

About: Women's College, Kolkata is a based out in . It is known for research contribution in the topics: Population & Breast cancer. The organization has 4552 authors who have published 5906 publications receiving 178809 citations.

An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein

Abstract: RING-finger proteins play crucial roles in ubiquitination events involved in diverse cellular processes including signal transduction, differentiation and apoptosis. Most of the RING-finger proteins have E3-ubiquitin ligase activity. RNF11 is a small RING-finger protein and harbors a RING-H2 domain and a PY motif that could facilitate protein:protein interaction(s) involved in oncogenesis. To isolate RNF11 protein partners and determine its role in normal and cancer cells, we performed yeast two-hybrid screening. Among 18 in-frame positive clones, three were found to be ZBRK1, Eps15 and AMSH (associated molecule with the SH3 domain of STAM). ZBRK1 is a KRAB domain containing Zinc-finger protein and is known to repress target gene transcription in a BRCA1-dependent manner. Eps15 is monoubiquitinated and is part of an essential complex involved in the endocytosis of plasma membrane receptors via the clathrin-mediated internalization pathway. Recent studies have shown that AMSH protein is involved in BMP/TGF-β signaling pathway by binding to Smad6 and Smad7. The association of RNF11 with these binding partners suggests that it would be involved in biological processes such as gene transcription, BMP/TGF-β signaling and ubiquitination-associated events. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. The potential functions of RNF11-mediated degradation of AMSH in breast cancer are discussed.

Enhanced susceptibility to pulmonary infection with Burkholderia cepacia in Cftr(-/-) mice.

Abstract: Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs of Cftr (m1unc-/-) (Cftr(-/-)) and congenic Cftr(+/+) controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptible Cftr(-/-) mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from the Cftr(-/-) mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages from Cftr(-/-) mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF.

Folate intakes and awareness of folate to prevent neural tube defects: A survey of women living in Vancouver, Canada

Abstract: Objective To estimate folate intake and knowledge in women of childbearing age, in relation to risk of neural tube defects. Subjects/setting One hundred forty-eight women (aged 18 to 45 years) in the Vancouver area of British Columbia, Canada. Design Using an interviewer-administered survey, we examined women for folate knowledge and the relation of folate knowledge to intake in a random sample. Contribution of folate from food, fortified grain products, and supplements was assessed by validated semiquantitative food frequency questionnaire. Statistical analyses performed Descriptive statistics, t tests, χ 2 , Pearson correlation analysis. Results Mean daily folate intake from food, fortified foods, and supplementation was 812±710 Dietary Folate Equivalents (DFE)/day. Fortification of bread and grain products contributed 104±68 μg synthetic folic acid (SFA)/day (equal to 174±114 DFE), and supplements contributed 205±388 μg SFA/day. Although 86% of women met the Estimated Average Requirement (320 DFE/day) for folate, only 26% met the recommendation (400 μg SFA/day) for women capable of becoming pregnant. Most (95%) of the women had heard of folate, but only 25% knew that it could prevent birth defects. One-fourth of the women had good or very good knowledge of folate-rich foods. However, folate knowledge was not related to its intake. The most common sources of folate information were magazines/newspapers, doctors, and television/radio. Lack of awareness of the importance of folate was the most common reason given for choosing not to use folic acid supplements before pregnancy. However, 78% of the women indicated that, with knowledge of the benefits of folate, they would use supplemental folic acid daily to reduce the risk of birth defects. Applications/conclusions Educational strategies are required to increase folate awareness among women and to promote the benefits of periconceptional folic acid supplementation. Targeting physicians to educate women on the importance of folate could be a potentially successful route. J Am Diet Assoc. 2003;103:181-185.