Regulation of pten activity by its carboxyl terminal autoinhibitoryChau Chan Lao
Regulation of PTEN Activity by Its Carboxyl-terminal Autoinhibitory Domain.
Leticia Odriozola, Gobind Singh, Thuong Hoang, and Andrew M. Chan
From the Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, 10029
THE JOURNAL OF BIOLOGICAL CHEMISTRY, VOL. 282, NO. 32, pp. 23306–23315, August 10, 2007
目前已知PTEN(Phosphatase and tensin homolog)是腫瘤抑制蛋白，其由403個氨基酸組成，主要分PTPase及C2 domain，C2 domain使PTEN可與細胞膜作用連結。
PTEN之C-tail(aa 350~403)被發現具有調控PTEN自身活性之功能。前人研究指出C-tail有6個可磷酸化之位置(Thr-366、Ser-370、Ser-380、Thr-382、Thr-383及Ser-385)，這些位置可調控PTEN之腫瘤抑制能力、胞內之分佈及穩定性。前人產生以上位置突變之PTEN變異株，發現這些變異株具有更強的腫瘤抑制能力，但穩定性將降低，這可能是因這些變異株具有更開放結構所致。
本報告針對研究PTEN C-tail在連結細胞膜和在其本身催化活性中扮演的功能。作者先產生一系列之PTEN磷酸化位置變異株，發現S385A會促使PTEN之membrane localization in vivo及加強phosphatase活性in vitro，而且此突變會使Ser-380/Thr-382/Thr-383 cluster的磷酸化程度降低，因此知Ser-385可透過被去磷酸化以調控PTEN。而以phosphomimic residues取代Ser-380/Thr-382/Thr-383會使上述S385A所產生之PTEN催化活性反轉。之後利用免疫沉澱方法，發現C-tail之71-amino acid region會與C2 domain上之CBR3 motif作用，暗示C-tail參與連結細胞膜之調控。最後利用合成之PTEN C-tail peptide，發現其可抑制PTEN之催化活性in vitro，而在細胞表現此peptide則會抑制PTEN之membrane localization，磷酸化之Akt量亦上升。以上實驗顯示C-tail在PTEN之membrane recruitment及PTPase活性調控中扮演Autoinhibitory domain角色。
The document discusses two scientific articles about factors that can lead to skin cancer and Ewing's sarcoma. The first article discusses how targeting the PTEN protein, which regulates cell growth, may help prevent skin cancer. The second article discusses how ultraviolet light can affect the function of the EWS protein involved in Ewing's sarcoma by changing the expression of genes it regulates and preventing an appropriate DNA damage response. The document emphasizes the importance of DNA repair mechanisms in protecting against UV radiation and preventing disease.
Regulation of pten activity by its carboxyl terminal autoinhibitoryChau Chan Lao
Regulation of PTEN Activity by Its Carboxyl-terminal Autoinhibitory Domain.
Leticia Odriozola, Gobind Singh, Thuong Hoang, and Andrew M. Chan
From the Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, 10029
THE JOURNAL OF BIOLOGICAL CHEMISTRY, VOL. 282, NO. 32, pp. 23306–23315, August 10, 2007
目前已知PTEN(Phosphatase and tensin homolog)是腫瘤抑制蛋白，其由403個氨基酸組成，主要分PTPase及C2 domain，C2 domain使PTEN可與細胞膜作用連結。
PTEN之C-tail(aa 350~403)被發現具有調控PTEN自身活性之功能。前人研究指出C-tail有6個可磷酸化之位置(Thr-366、Ser-370、Ser-380、Thr-382、Thr-383及Ser-385)，這些位置可調控PTEN之腫瘤抑制能力、胞內之分佈及穩定性。前人產生以上位置突變之PTEN變異株，發現這些變異株具有更強的腫瘤抑制能力，但穩定性將降低，這可能是因這些變異株具有更開放結構所致。
本報告針對研究PTEN C-tail在連結細胞膜和在其本身催化活性中扮演的功能。作者先產生一系列之PTEN磷酸化位置變異株，發現S385A會促使PTEN之membrane localization in vivo及加強phosphatase活性in vitro，而且此突變會使Ser-380/Thr-382/Thr-383 cluster的磷酸化程度降低，因此知Ser-385可透過被去磷酸化以調控PTEN。而以phosphomimic residues取代Ser-380/Thr-382/Thr-383會使上述S385A所產生之PTEN催化活性反轉。之後利用免疫沉澱方法，發現C-tail之71-amino acid region會與C2 domain上之CBR3 motif作用，暗示C-tail參與連結細胞膜之調控。最後利用合成之PTEN C-tail peptide，發現其可抑制PTEN之催化活性in vitro，而在細胞表現此peptide則會抑制PTEN之membrane localization，磷酸化之Akt量亦上升。以上實驗顯示C-tail在PTEN之membrane recruitment及PTPase活性調控中扮演Autoinhibitory domain角色。
The document discusses two scientific articles about factors that can lead to skin cancer and Ewing's sarcoma. The first article discusses how targeting the PTEN protein, which regulates cell growth, may help prevent skin cancer. The second article discusses how ultraviolet light can affect the function of the EWS protein involved in Ewing's sarcoma by changing the expression of genes it regulates and preventing an appropriate DNA damage response. The document emphasizes the importance of DNA repair mechanisms in protecting against UV radiation and preventing disease.
A journal club style presentation on a publication about the effect of microRNAs and pseudogenes on tumor gene regulation.
(Note: The animations in the slides do not work on SlideShare, please download the PowerPoint file to view.)
La fractura del epicóndilo medial es una lesión frecuente en pediatría que ocurre más comúnmente en adolescentes varones. Existen controversias sobre el tratamiento, pero generalmente se recomienda el manejo quirúrgico para fracturas expuestas, luxaciones irreductibles, fragmentos intraarticulares o inestabilidad en valgo. Los estudios a largo plazo muestran buenos resultados funcionales independientemente del tratamiento, con desviaciones axiales menores a 9 grados y déficit de movimiento menor a 19 grados, además de fuerza muscular
The document provides an introduction and outline for a presentation on immunosuppression for transplantation. It discusses the history of immunosuppression, mechanisms of transplant rejection, categories of immunosuppressant agents including induction agents, calcineurin inhibitors like cyclosporine and tacrolimus, antiproliferative agents, side effects and drug interactions of immunosuppressants, and monitoring of drug levels. The presentation aims to provide an overview of current immunosuppression protocols and management of side effects.
This document discusses various classes of immunosuppressant drugs used to prevent rejection of transplanted organs or treat autoimmune diseases. It describes glucocorticoids, calcineurin inhibitors like cyclosporine and tacrolimus, mTOR inhibitors like sirolimus and everolimus, antiproliferative agents, biological agents targeting cytokines like TNF inhibitors, monoclonal antibodies, adhesion molecule inhibitors, and tolerogens. Specific drugs are discussed within each class along with their mechanisms of action, pharmacokinetics, and adverse effects.
The PTEN and PI3-Kinase Pathway in Cancer pptBernard Bahaah
The document presents information on PTEN and the PI3-kinase pathway in cancer. It discusses how PTEN acts as a tumor suppressor by negatively regulating the PI3-kinase pathway, which promotes cell growth and survival. Mutations or deletions of the PTEN gene are common in many cancer types as they lead to overactivation of the PI3-kinase pathway. The document outlines the signaling events in the PI3-kinase pathway, how PTEN regulates it, additional functions of PTEN, and potential cancer therapeutics that target this pathway.
Immunosuppression involves reducing the activation of the immune system through medications, surgery, radiation or other means. The document discusses the history of immunosuppression and developments in transplantation including the identification of cortisone and research on the immune system. It outlines current methods of immunosuppression including calcineurin inhibitors, mTOR inhibitors, antimetabolites, corticosteroids, depleting antibodies and fusion proteins. The mechanisms, types and treatment of allograft rejection such as hyperacute, acute and chronic rejection are also summarized.
Alex Rosenberg is an Intensivist who was working in a transplant centre last year. He gave this talk on immunosupression at last year's Bedside Critical Care Conference and managed to make a fairly dry subject seem understandable and relevant. Go to www.intensivecarenetwork.com for the podcast.
Tumor suppressor genes regulate cell growth and division. When functioning properly, they inhibit tumor formation but when mutated or inactivated, they lose this ability. Examples include p53, Rb, APC, BRCA1, BRCA2. p53 is mutated in 50% of cancers and regulates DNA repair/cell cycle arrest or apoptosis. Li-Fraumeni syndrome results from germline p53 mutations increasing cancer risk. The APC gene regulates beta-catenin to control cell growth. Mutations in tumor suppressor genes are often required for tumor development according to the two-hit hypothesis as seen with retinoblastoma caused by Rb mutations.
describe the tumor suppressor genes and examples for downloading the presentation, more presentations , infographics and blogs visit :
studyscienceblog.wordpress.com
Conventional and non Conventional ResourcesTriambak Sahai
Conventional resources like coal, oil and natural gas are traditional energy sources that form over long periods from decaying organic matter. However, they release greenhouse gases when burned. Non-conventional resources such as solar, wind, hydropower and geothermal are increasingly important as they are renewable, pollution-free alternatives to conventional sources. Non-conventional energy comes from ongoing natural processes like sunlight, wind and tides rather than finite fossil fuels.
Tumor suppressor genes help repair damaged DNA and inhibit cell proliferation and cancer growth. They fall into two categories: caretaker genes that maintain genome integrity through DNA repair, and gatekeeper genes that inhibit proliferation or promote death of cells with damaged DNA. Key tumor suppressor genes include p53, Rb, APC, WT1, NF1, VHL, p15, p16, BRCA1, BRCA2, and PTEN. Mutation of both copies of a tumor suppressor gene, as with the two-hit hypothesis for retinoblastoma, can lead to uncontrolled cell growth and cancer development.
This document provides an overview of tumor immunology, including definitions of cancer and carcinogenesis, tumor antigens, the immune response to cancer, and mechanisms by which tumors escape the immune system. It discusses how tumors stimulate an immune response through antigens but also ways they can evade immunity, such as through low immunogenicity, antigen modulation, and immune suppression. It describes experimental evidence for tumor antigens and the immune response against tumors.
The document discusses the makhaarij (places of articulation) of Arabic letters from which sounds emanate when pronouncing each letter. It explains that the 29 letters of the Arabic alphabet are pronounced from 17 different makhaarij in the throat, palate, teeth or lips. It provides a table listing the place of articulation, names and corresponding letters for each category of makhaarij. The purpose is to understand proper pronunciation of each letter according to its unique place of origin in the mouth.
