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Articles 1 - 5 of 5

Full-Text Articles in Cell Biology

Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, Nomeda Girnius, Roger J. Davis Nov 2017

Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, Nomeda Girnius, Roger J. Davis

UMass Metabolic Network Publications

Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that ...


Regulation Of Ripk1 Activation By Tak1-Mediated Phosphorylation Dictates Apoptosis And Necroptosis, Jiefei Geng, Yasushi Ito, Linyu Shi, Palak Amin, Jiachen Chu, Amanda Tomie Ouchida, Adnan Kasim Mookhtiar, Heng Zhao, Daichao Xu, Bing Shan, Ayaz Najafov, Guangping Gao, Shizuo Akira, Junying Yuan Aug 2017

Regulation Of Ripk1 Activation By Tak1-Mediated Phosphorylation Dictates Apoptosis And Necroptosis, Jiefei Geng, Yasushi Ito, Linyu Shi, Palak Amin, Jiachen Chu, Amanda Tomie Ouchida, Adnan Kasim Mookhtiar, Heng Zhao, Daichao Xu, Bing Shan, Ayaz Najafov, Guangping Gao, Shizuo Akira, Junying Yuan

Open Access Articles

Stimulation of TNFR1 by TNFalpha can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFalpha-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulating this critical decision. Using phospho-Ser321 as a marker, we show that the transient phosphorylation of RIPK1 intermediate domain induced by TNFalpha leads to RIPK1-independent apoptosis when NF-kappaB activation is inhibited by cycloheximide. On the other hand, blocking Ser321 phosphorylation promotes RIPK1 activation and its interaction with FADD to mediate RIPK1-dependent apoptosis (RDA ...


Killers Creating New Life: Caspases Drive Apoptosis-Induced Proliferation In Tissue Repair And Disease, Caitlin E. Fogarty, Andreas Bergmann Aug 2017

Killers Creating New Life: Caspases Drive Apoptosis-Induced Proliferation In Tissue Repair And Disease, Caitlin E. Fogarty, Andreas Bergmann

Open Access Articles

Apoptosis is a carefully orchestrated and tightly controlled form of cell death, conserved across metazoans. As the executioners of apoptotic cell death, cysteine-dependent aspartate-directed proteases (caspases) are critical drivers of this cellular disassembly. Early studies of genetically programmed cell death demonstrated that the selective activation of caspases induces apoptosis and the precise elimination of excess cells, thereby sculpting structures and refining tissues. However, over the past decade there has been a fundamental shift in our understanding of the roles of caspases during cell death-a shift precipitated by the revelation that apoptotic cells actively engage with their surrounding environment throughout the ...


Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw May 2017

Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw

UMass Metabolic Network Publications

The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to ...


Genetic Disruption Of Oncogenic Kras Sensitizes Lung Cancer Cells To Fas Receptor-Mediated Apoptosis, Haiwei Mou, Jill Moore, Sunil K. Malonia, Yingxiang Li, Deniz M. Ozata, Soren Hough, Chun-Qing Song, Jordan L. Smith, Andrew H. Fischer, Zhiping Weng, Michael R. Green, Wen Xue Apr 2017

Genetic Disruption Of Oncogenic Kras Sensitizes Lung Cancer Cells To Fas Receptor-Mediated Apoptosis, Haiwei Mou, Jill Moore, Sunil K. Malonia, Yingxiang Li, Deniz M. Ozata, Soren Hough, Chun-Qing Song, Jordan L. Smith, Andrew H. Fischer, Zhiping Weng, Michael R. Green, Wen Xue

Program in Bioinformatics and Integrative Biology Publications and Presentations

Genetic lesions that activate KRAS account for approximately 30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form ...