Negative Regulation of JNK Signaling by the Tumor Suppre：由肿瘤抑制JNK信号的负调控.pptVIP

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2018-06-30 发布于浙江
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Negative Regulation of JNK Signaling by the Tumor Suppre：由肿瘤抑制JNK信号的负调控.ppt

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Negative Regulation of JNK Signaling by the Tumor Suppre：由肿瘤抑制JNK信号的负调控

Negative Regulation of JNK Signaling by the Tumor Suppressor CYLD The Journal of Biological Chemistry Authors: William Reily, Minying Zhang, and Shao-Cong Sun Presentors: Ronesha Franklin Kimberly Kimbrough Objective of Experiment To investigate the function of endogenous CYLD in the regulation of cell signaling. What is CYLD? CYLD is a tumor suppressor that is mutated in familial cylindromatosis. Familial cylindromatosis is a genetic syndrome in which numerous benign tumors of skin adnexa develop, principally on the head and neck. This disorder is inherited in an autosomal manner and is caused by mutation of CYLD gene on chromosome 16q12-q13. Results in a pile up of cells. CYLD Functions CYLD Is a deubiquitinating enzyme that negatively regulates NFkB activation by TNFR family members. Deubiquitinating enzymes remove ubiqutin, a small molecule that serves as a tag that signals proteins to proteasomes for degradation. Inhibits the ubiquitnation of certain signaling molecules, including members of the tumor necrosis factor receptor-associated factor (TRAF) family. TRAF Function TRAFs activate downstream signaling cascades and lead to activation of IKK and 3 families of MAPKs: JNK Extracellular signal responsive kinase P38 JNK Functions JNK functions include regulation of immune and inflammatory responses, cell growth, apoptosis, and tumor formation. JNK Activation Activation of JNK is mediated by a kinase cascade involving MAPK kinase and MAPK kinase kinase. Two MAPK kinase, MKK4 MKK7 is required for JNK activation by inflammatory cytokines, whereas MKK4 is more important for JNK activation by stress signals. Overview of Materials and Methods 293 cells (human embryonic kidney cells) were transected with either the empty vector pcDNA or an expression vector encoding HA-tagged CYLD. About 7 micrograms of protein lysates were subjected to IB using anti-CYLD. The transected HA-CYLD, endogenous CYLD, and some nonspecific protein bands are indicated.