Post Transcriptional Regulation Of Plasminogen Activator Inhibitor Type 2 Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$318,000.00
Summary
The process of wound healing, cell migration and the spread of cancers requires the recruitment of specialised proteases to the cell surface . These proteases act to degrade other proteins, mainly in the extracellular space, which in turn allows cells to move around, wounds to close, and blood clots to disappear. The plasminogen activating system is one of the enzyme systems involved in these events. One of the proteases that cleaves plasminogen to its active form, plasmin, is urokinase (u-PA) a ....The process of wound healing, cell migration and the spread of cancers requires the recruitment of specialised proteases to the cell surface . These proteases act to degrade other proteins, mainly in the extracellular space, which in turn allows cells to move around, wounds to close, and blood clots to disappear. The plasminogen activating system is one of the enzyme systems involved in these events. One of the proteases that cleaves plasminogen to its active form, plasmin, is urokinase (u-PA) and the activity of u-PA is regulated by its natural inhibitor called plasminogen activator inhibitor type 2 (PAI-2). u-PA is strongly implicated in the progression of metastatic cancer and high levels of PAI-2 relative to u-PA is regularly seen as a positive prognostic indicator for metastatic cancer. In this situation, PAI-2 acts to limit the activity of u-PA thereby restricting the migration potential of the cancer. PAI-2 is unusual because it exists both inside and outside the cell. Outside the cell, PAI-2 acts to inhibit u-PA activity, while inside the cell, PAI-2 also plays a role in the inhibition of cell growth and differentiation. It is therefore important to understand how the production of PAI-2 is regulated in cells. A significant component of PAI-2 regulation occurs post-transcriptionally, particularly at the level of mRNA stability. We have identified some of the proteins that bind to PAI-2 mRNA and influence its longevity in the cell. This project aims to further undertand how these as well as other PAI-2 mRNA binding proteins influence the expression of the PAI-2 gene.Read moreRead less
Post-transcriptional Regulation Of Plasminogen Activator Inhibitor 2 Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$508,838.00
Summary
Plasminogen activator inhibitor type 2 (PAI-2) is a protease inhibitor that has intracellular and extracellular functions. The PAI-2 gene is highly regulated at the level of PAI-2 mRNA stability. We have identified regions within the PAI-2 transcript essential for this regulation and a number of novel proteins that engage these regions. This project is aimed at understanding how these and other proteins control PAI-2 expression at the mRNA level.
The Interferon Inducible Transcription Factor IFI 16.
Funder
National Health and Medical Research Council
Funding Amount
$151,208.00
Summary
Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein pro ....Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein products of these genes in turn directly or indirectly mediate the necessary biological response to maintain cellular homeostasis. While there are hundreds of cellular genes that are induced following IFN stimulation, the molecular and biological functions of the protein products of many of these genes are often not known. IFI 16 is one such IFN-induced gene that belongs to a family of related genes found in human and mouse. Little is known about what role IFI 16 may play in an IFN response and how it may function to mediate its effect. The proposed study is aimed at understanding how IFI 16 is upregulated following treatment of cells with IFN, identifying which cellular genes may be directly regulated by IFI 16 and how this happens, and whether IFI 16 plays a role in the development of specific blood cells.Read moreRead less