title: Syntaxin 6, a regulator of the protein trafficking machinery and a target of the p53 family, is required for cell adhesion and survival.
abstract: The p53 family consists of p53, p63, and p73. It has been well characterized that all of the p53 family proteins are transcription factors and capable of regulating cell cycle and apoptosis. To determine whether the p53 family exerts tumor suppression by other mechanisms, we set to identify novel p53 family target genes. Here, we found that the gene encoding STX6 (syntaxin 6), a vesicle transporter protein, is directly regulated by each of the p53 family proteins. In addition, STX6 can be induced by DNA damage and Mdm2 inhibitor Nutlin-3 in a p53-dependent manner. To examine how STX6 mediates the activity of the p53 family, STX6 is inducibly overexpressed or knocked down in various cell lines. We found that overexpression of STX6 alone has limited effect on cell proliferation. In contrast, we found that knockdown of STX6 inhibits cell proliferation and survival. We also found that knockdown of STX6 leads to cell cycle arrest and apoptosis. Interestingly, we found that p53 is necessary for STX6 knockdown-induced cell cycle arrest and apoptosis. Furthermore, we found that STX6 is necessary for proper expression of focal adhesion kinase and integrin alpha5 adhesion receptor. Consistent with this observation, STX6 knockdown inhibits cell adhesion. Together, we postulate that STX6 is an effector and a modulator of the p53 family in the regulation of cell adhesion and survival.
authors.affiliation: Center for Comparative Oncology, University of California, Davis, California 95616, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Shu
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D007093:Imidazoles; D039564:Integrin alphaV; D009687:Nuclear Proteins; D010879:Piperazines; D050765:Qa-SNARE Proteins; C000612950:STX6 protein, human; C495901:TP53 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C482205:nutlin 3; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
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