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Full-Text Articles in Life Sciences
Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen
Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen
Markey Cancer Center Faculty Publications
Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …
Phlpp Negatively Regulates Cell Motility Through Inhibition Of Akt Activity And Integrin Expression In Pancreatic Cancer Cells, Alena J. Smith, Yang-An Wen, Payton D. Stevens, Jingpeng Liu, Chi Wang, Tianyan Gao
Phlpp Negatively Regulates Cell Motility Through Inhibition Of Akt Activity And Integrin Expression In Pancreatic Cancer Cells, Alena J. Smith, Yang-An Wen, Payton D. Stevens, Jingpeng Liu, Chi Wang, Tianyan Gao
Markey Cancer Center Faculty Publications
Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Malignant progression of pancreatic cancer depends not only on rapid proliferation of tumor cells but also on increased cell motility. In this study, we showed that increased PHLPP expression significantly reduced the rate of migration in pancreatic ductal adenocarcinoma (PDAC) cells whereas knockdown of PHLPP had the opposite effect. In addition, cell motility at the individual cell level was negatively regulated by PHLPP as determined using time-lapse imaging. Interestingly, the expression of β1 and β4 integrin proteins were decreased in PHLPP overexpressing cells and increased in PHLPP knockdown cells …
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers
Markey Cancer Center Faculty Publications
Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …
Sonic Hedgehog Dependent Phosphorylation By Ck1Α And Grk2 Is Required For Ciliary Accumulation And Activation Of Smoothened, Yongbin Chen, Noriaki Sasai, Guoqiang Ma, Tao Yue, Jianhang Jia, James Briscoe, Jin Jiang
Sonic Hedgehog Dependent Phosphorylation By Ck1Α And Grk2 Is Required For Ciliary Accumulation And Activation Of Smoothened, Yongbin Chen, Noriaki Sasai, Guoqiang Ma, Tao Yue, Jianhang Jia, James Briscoe, Jin Jiang
Markey Cancer Center Faculty Publications
Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo), but how vertebrate Smo is activated remains poorly understood. In Drosophila, Hh dependent phosphorylation activates Smo. Whether this is also the case in vertebrates is unclear, owing to the marked sequence divergence between vertebrate and Drosophila Smo (dSmo) and the involvement of primary cilia in vertebrate Hh signaling. Here we demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. We demonstrate that …