LKB1 negatively regulates AKT1 signaling via DBC1 and TRB3
Andrabi, S.; Sarwar, Z.; Bhat, S. A.; Gillani, S. Q.; Reshi, I.; Un Nisa, M.; Adelmant, G.; Marto, J.
Show abstract
DBC1 plays a critical role in various cellular functions notably cell proliferation, transcription, histone modification and adipogenesis. Current reports about the role of DBC1 in tumorigenesis are paradoxical and designate DBC1 both as a tumor suppressor or an oncogene. Here, using small T antigen of polyoma virus (PyST) as a tool, we have delineated a signaling mechanism that connects LKB1 to AKT1 via DBC1. We report that PyST associates with DBC1 and leads to its down-regulation. Our results also show that PyST expression promotes LKB1 activation which in turn leads to in the downregulation of DBC1 protein. Absence of DBC1 results in transcriptional upregulation and consequently enhanced protein levels of TRB3. TRB3 sequesters AKT1, and consequently the phosphorylation and activity of AKT1 is compromised. This ultimately results in inactivation of pro-survival pathways triggered via AKT1 signaling. Our studies thus provide an insight into a signaling pathway that connects LKB1, DBC1, TRB3 and AKT1.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation 94%
- SET8 localization to chromatin flanking DNA damage is dependent on RNF168 ubiquitin ligase 91%
- Fate of the M-phase-assembled centrioles during the cell cycle in the TP53;PCNT;CEP215-deleted cells 91%
Similar papers in this journal
- Tumors cells with mismatch repair deficiency induce hyperactivation of Pyroptosis resistant to cell membrane damage but are more sensitive to Co-treatment of IFN-γ and TNF-α to PANoptosis 94%
- The oncogenic E3 ligase TRIP12 suppresses epithelial-mesenchymal transition (EMT) and metastasis-related processes through ZEB1/2 94%
- CDK8/19 Inhibition Attenuates G1 Arrest Induced by BCR-ABL Antagonists and Accelerates Death of Chronic Myelogenous Leukemia Cells 93%
Similar papers in this journal
Similar papers in this journal
- eIF2α integrates proteotoxic signals both from ER and cytoplasm: Hsp70-Bag3 module regulates HRI-dependent phosphorylation of eIF2α 95%
- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A 94%
- A Non-genetic Mechanism for Chemoresistance in Lung Cancer: The Role of Integrin β4/Paxillin Axis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.