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Full-Text Articles in Cancer Biology
Pi3k/Akt Signaling Activates Hsf1 To Preserve Proteostasis And Sustain Growth, Zijian Tang
Pi3k/Akt Signaling Activates Hsf1 To Preserve Proteostasis And Sustain Growth, Zijian Tang
Electronic Theses and Dissertations
Signaling through oncogenic PI3K/AKT kinase pathway is crucial to cell and organ growth. Phosphorylation by AKT has long been perceived as a key factor to enhance protein biosynthesis that enables cell growth and survival. Here, we report that HSF1, the master regulator of the proteotoxic stress response (PSR), is a new AKT substrate. Beyond mobilizing the PSR under heat shock, the AKT-mediated HSF1 activation supports robust growth. In a mouse model of human megalencephaly, expression of a constitutively active PI3KCAsuffices to drive brain overgrowth, and strikingly, it also provokes proteomic chaos including protein aggregation and amyloidogenesis. Deletion of Hsf1 …
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Dissertations & Theses (Open Access)
Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Theses and Dissertations
Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein …