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Full-Text Articles in Cells

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar May 2014

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar

Theses and Dissertations (ETD)

The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …


Physical And Functional Coupling Of Cftr And Pde3a, Himabindu Penmatsa Dec 2009

Physical And Functional Coupling Of Cftr And Pde3a, Himabindu Penmatsa

Theses and Dissertations (ETD)

Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrated that phosphodiesterase type 3A (PDE3A) is physically and functionally coupled to cystic fibrosis transmembrane conductance regulator (CFTR). PDE3A inhibition increases cyclic adenosine 3′, 5′-monophosphate (cAMP) levels in a compartmentalized manner at the plasma membrane, which potentiates CFTR channel function and further clusters PDE3A and CFTR into microdomains. Actin skeleton disruption reduces PDE3A-CFTR interaction; segregates PDE3A from its interacting partners thus compromise the integrity of the macromolecular complex. Consequently, PDE3A inhibition no longer activates CFTR channel function in …


Golgi Specificity And Development Of Autoreactive B Cells, Fazlullah Salar Khan Nawazi May 2008

Golgi Specificity And Development Of Autoreactive B Cells, Fazlullah Salar Khan Nawazi

Theses and Dissertations (ETD)

B cell receptors with certain heavy/light chain pairs predominate in the periphery of anti-DNA heavy chain transgenic mice while certain other B cell receptors are absent. We wanted to know why. To answer this, we re-constructed B cell receptors represented in the anti-DNA transgenic mice by cloning them as single chain variable fragments (scFv) to analyze their affinity to dsDNA. scFv representing receptors that were recovered from the spleens of transgenic mice had very little to no affinity to dsDNA. scFv representing receptors that were absent in the spleen had high affinity to dsDNA. We therefore concluded that receptors with …


Probing The Role Of Nascent Helicity In Protein Function: P27kip1 As A Regulator Of The Cell Cycle, Steve Otieno May 2007

Probing The Role Of Nascent Helicity In Protein Function: P27kip1 As A Regulator Of The Cell Cycle, Steve Otieno

Theses and Dissertations (ETD)

p27kip1 binds to and regulates the activity of cyclin-dependent kinases (Cdks) which are the master timekeepers of the cell division cycle. Members of the p27 family of proteins, also including p21 and p57, are called cyclin-dependent kinase inhibitors (CKIs). The amino terminal domain of p27 inhibits Cdk activity and is referred to as the kinase inhibitory domain (KID). The KID is comprised of a cyclin-binding domain (D1) and a Cdk binding domain (D2) joined by a 22 residue linker domain (LH). Structural analysis of the KID in solution before binding its Cdk targets revealed that D1 and D2 are …


Cellular Expression Of Ionotropic Glutamate Receptor Subunits On Specific Striatal Neuron Types And Its Implication For Striatal Vulnerability In Glutamate Receptor-Mediated Excitotoxicity, Quan Chen Jan 1996

Cellular Expression Of Ionotropic Glutamate Receptor Subunits On Specific Striatal Neuron Types And Its Implication For Striatal Vulnerability In Glutamate Receptor-Mediated Excitotoxicity, Quan Chen

Theses and Dissertations (ETD)

No abstract provided.