CK2 is a ubiquitous serine/threonine protein kinase implicated in numerous cellular processes as well as in tumorigenesis. CK2 is composed of two catalytic (αα, αα’, α’α’) subunits and two regulatory (ββ) subunits that assemble to form the active CK2 holoenzyme. CK2 has been shown to phosphorylate, interact with, and regulate other proteins, including other protein kinases. CK2 substrates can be initially bound by the CK2β regulatory subunit, which acts as a docking site to facilitate phosphorylation and mediate CK2 substrate specificity. In a screen to identify novel CK2β interacting proteins, I identified three novel CK2β interactors, including the mitogen- and stress-activated kinase 2 (MSK2), which I pursued for further characterization. MSK2, and the closely related isoform MSK1, are nuclear kinases that are activated following mitogen stimulation or cellular stress, including UV radiation, by the ERK1/2 and p38-MAPK signaling cascades, respectively. However, factors that differentially regulate MSK1 and MSK2 have not been well characterized. In my thesis, I demonstrate that CK2, which contributes to NF-κB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue serine-324 and when substituted to alanine (S324A) also compromised MSK2 activity. RNA interference-mediated depletion of MSK2 in human MDA-MB-231 cells, but not MSK1 depletion, resulted in impaired UV-induced phosphorylation of NF-κB p65 at serine-276 in vivo, which was restored by the ectopic expression of MSK2 but not by MSK2-S324A. Furthermore, UV-induced p65 transactivation capacity was dependent on MSK2, MSK2 residue S324, and p65-S276. These results suggest that MSK1 and MSK2 are differentially regulated by CK2 during the UV response and that MSK2 is the major protein kinase responsible for the UV-induced phosphorylation of p65 at S276 that positively regulates NF-κB activity in MDA-MB-231 cells.

CK2 is a ubiquitous serine/threonine protein kinase implicated in numerous cellular processes as well as in tumorigenesis. CK2 is composed of two catalytic (αα, αα’, α’α’) subunits and two regulatory (ββ) subunits that assemble to form the active CK2 holoenzyme. CK2 has been shown to phosphorylate, interact with, and regulate other proteins, including other protein kinases. CK2 substrates can be initially bound by the CK2β regulatory subunit, which acts as a docking site to facilitate phosphorylation and mediate CK2 substrate specificity. In a screen to identify novel CK2β interacting proteins, I identified three novel CK2β interactors, including the mitogen- and stress-activated kinase 2 (MSK2), which I pursued for further characterization. MSK2, and the closely related isoform MSK1, are nuclear kinases that are activated following mitogen stimulation or cellular stress, including UV radiation, by the ERK1/2 and p38-MAPK signaling cascades, respectively. However, factors that differentially regulate MSK1 and MSK2 have not been well characterized. In my thesis, I demonstrate that CK2, which contributes to NF-κB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue serine-324 and when substituted to alanine (S324A) also compromised MSK2 activity. RNA interference-mediated depletion of MSK2 in human MDA-MB-231 cells, but not MSK1 depletion, resulted in impaired UV-induced phosphorylation of NF-κB p65 at serine-276 in vivo, which was restored by the ectopic expression of MSK2 but not by MSK2-S324A. Furthermore, UV-induced p65 transactivation capacity was dependent on MSK2, MSK2 residue S324, and p65-S276. These results suggest that MSK1 and MSK2 are differentially regulated by CK2 during the UV response and that MSK2 is the major protein kinase responsible for the UV-induced phosphorylation of p65 at S276 that positively regulates NF-κB activity in MDA-MB-231 cells.

Organic electronics have reached the level of commercialization and are important parts of our daily life. They are integrated into portable computers, cell phones, identification cards, television, cars, etc. The organic thin film transistors (OTFTs) are the most attractive organic electronic elements that have applications as electronic flexible paper, sensors, smart cards, erasable memory devices, RF-ID tags, and in backplanes for OLED displays. Their performance has already exceeded the performance of transistors based on the amorphous silicon (α-Si). Organic thin film phototransistors (OPTs) have attracted significant research attention as functional OTFTs due to the unique structure of OTFTs (three-terminal device) complemented with the light (fourth terminal). The OTFTs structure enables modulation and amplification of the output signal (the drain current) while light gives the functionality and enhances the performance. Compared to organic photodiodes, OPTs have higher sensitivity and lower noise due to the OTFT structure. Additionally, the advantage of OPTs over inorganic PTs lays in a variety of light responsive organic materials that can be used as active channel materials. Accordingly, use of organic compounds enabled OPTs fabrication from solution, melt, and printing, over large areas of plastic substrates with which they are compatible. So far, many researchers have reported high-performance OPTs. Typically, synthesis of the new light receiving/emitting semiconducting materials is the common approach for the OPT development. Another way is to engineer the device structure by introducing new layers with different functionalities. Often, synthesis is costly, complex, lengthy, and not industrially feasible. This thesis focuses on the development of new methods and materials for OPT performance enhancement to avoid lengthy synthesis and fabrication processes. According to the layers in a typical OPT, that is, from the top to the bottom: active channel, channel/gate dielectric interface, and the gate dielectric layer, the thesis has three major focuses: engineering of the active channel for high-performance OPTs using existing small molecule and existing or new dielectric polymeric materials (Chapters 3-5), interface engineering (Chapter 6), and engineering of the gate dielectric layer (Chapter 7). Utilizing blends of a UV-A responsive 2,7-dipentyl[1]benzothieno[3,2-b][1]benzothiophene (C5-BTBT) small molecule semiconductor and various dielectric polymers (polyesters, PMMA, PVAc, PS, and PC) we developed highly photoresponsive and photosensitive OPTs. Furthermore, we designed and synthesized a new polyimide that is soluble, thermally stable, with reduced deep coloration and more importantly with the strong electron withdrawing groups. High-performance and highly photosensitive OPTs were achieved with capabilities of the application as photo memory elements characteristic of fast switching and long retention times of the persistent photocurrent. We demonstrated that by simple channel/dielectric interface modification using organosilanes with different end groups, the drain photocurrent, and hole mobility could be modulated and enhanced under the UV light illumination. In the final part, we demonstrated that both active channel and dielectric layer engineering could synergistically enhance the performance of OPTs for potential fabrication as photo memory elements. This thesis contributed significantly to fundamental knowledge of photoresponsive organic electronic devices and application of OPTs in the area of printed and flexible electronics / Thesis / Doctor of Philosophy (PhD) / Organic electronics have become a part of our daily life since they are integrated into cell phones, computers, TVs, displays, etc. Their advantage is their versatility due to a variety of organic compounds that can be used as semiconductors for the specific applications, low-cost processing methods (solution, printing, and melt) and large-area flexible substrates that can be used for their fabrication. For the same reasons, organic phototransistors are very attractive for modern optoelectronics. Generally, in this study, we developed and demonstrated new strategies of developing an organic phototransistor and enhancing/optimizing its performance. Firstly, we developed semiconducting blends that are responsive to UV-A light when integrated into an organic phototransistor. Secondly, by channel/gate dielectric interface manipulation we demonstrated control over photoelectrical properties of the organic phototransistor and discovered mechanisms of the enhancement. Thirdly, we optimized and developed reliable, high-performance, and highly UV responsive organic phototransistors with potential application as a photo memory element