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Full-Text Articles in Life Sciences

Cx43 Reduces Melanoma Growth Within A Keratinocyte Microenvironment And During Tumorigenesis In Vivo, Mark J. Ableser Aug 2013

Cx43 Reduces Melanoma Growth Within A Keratinocyte Microenvironment And During Tumorigenesis In Vivo, Mark J. Ableser

Electronic Thesis and Dissertation Repository

Connexins have been frequently identified as tumor suppressors in many cancers, however, their role in melanoma tumorigenesis remains controversial. Here, we show that B16-BL6 mouse melanoma cells express low levels of Cx26 and Cx43, rendering them gap junctional intercellular communication (GJIC) deficient. Following ectopic expression of Cx26 and Cx43, gap junction-like plaques were evident at the cell surface and the incidence of dye transfer was significantly increased similar to connexin-rich keratinocytes. The expression of Cx43, but not Cx26, significantly reduced proliferation and anchorage-independent growth relative to controls, whereas migration was unaffected. Additionally, Cx43-expressing melanoma cells displayed significantly reduced growth amongst ...


The Role Of K63-Linked Ubiquitination Cycles In Akt Kinase Activation, Wei-Lei Yang Aug 2013

The Role Of K63-Linked Ubiquitination Cycles In Akt Kinase Activation, Wei-Lei Yang

UT GSBS Dissertations and Theses (Open Access)

Akt (also known as protein kinase B) serves a central regulator in PI3K/Akt signaling pathways to regulate numerous physiological functions including cell proliferation, survival and metabolism. Akt activation requires the binding of Akt to phospholipid PIP3 on the plasma membrane and subsequent phosphorylation of Akt by its kinases. Growth factor-mediated membrane recruitment of Akt is a crucial step for Akt activation. However, the mechanism of Akt membrane translocation is unclear. Protein ubiquitination is a significant posttranslational modification that controls many biological functions such as protein trafficking and signaling activation. Therefore, we hypothesize that ubiquitination may be involved in Akt ...


The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson Jan 2013

The Role Of Tipe2 In The Regulation Of Inflammation And Tumorigenesis, Derek Johnson

Publicly Accessible Penn Dissertations

TIPE2 is a recently discovered regulator of immunity and inflammation. Here we describe a new function of TIPE2 in the regulation of Ras signaling and Tumorigenesis. By using various stimuli and inhibitors in T Cells and macrophages we discovered that TIPE2 is regulated at both the message and protein level by inflammatory stimuli. TIPE2 mRNA is regulated in the short to intermediate term by an NF-Kappa B induced micro RNA, and TIPE2 is also ubiquitylated and degraded, possibly by SCF-Beta TRCP. Mechanistically TIPE2 interacts with and inhibits the Ras-interacting domain of the RalGDS family of Ras effectors, leading to a ...