Molecular Biology Commons^™

Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai

Dissertations

Prostaglandin F2α (PGF2α) is a potent physiological inhibitor of adipocyte differentiation. In previous studies, we demonstrated that PGF2α inhibits adipogenesis via activation of the calcium-regulated protein phosphatase, calcineurin. In this current study, we have now extended these findings to identify the IL-11 cytokine and the Nurr1 orphan nuclear hormone receptor as functionally important downstream transcriptional targets of the PGF2α/calcineurin-pathway involved in the inhibition of adipocyte differentiation. In the case of IL-11, we show that this cytokine acts in an autocrine fashion to inhibit adipogenesis via the essential actions of the gp130 cytokine co-receptor signaling subunit. Further, by using a well-characterized …

The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken

Dissertations

The AF9 protein is one of the most common chromosomal translocation partners of the MLL gene in MLL leukemia. Wild-type AF9 is a member of the pTEFb transcription elongation complex, and interacts with gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are retained in the oncogenic MLL-AF9 fusion protein, and may be required for leukemic transformation.

Using bone marrow progenitor cells isolated from conditional Af9 knockout mice, we examined in vitro differentiation of hematopoietic progenitor cells to the erythroid, myeloid and megakaryocytic lineages in the presence or absence of Af9. Based on previously published studies, we …