Sandbox Reserved 829: Difference between revisions
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Nuclear translocation of transcription factors is a crucial requirement for their action and stimulus-dependent nuclear translocation can serve as a mechanism to regulate gene expression at the level of transcription initiation. | Nuclear translocation of transcription factors is a crucial requirement for their action and stimulus-dependent nuclear translocation can serve as a mechanism to regulate gene expression at the level of transcription initiation. | ||
NLS is composed of several basic amino acids such as arginine (R) and lysine (K), as we can see in the NLS sequence RRMKWKK of PDX-1. This motif is sufficient for the nuclear import of PDX-1. | NLS is composed of several basic amino acids such as arginine (R) and lysine (K), as we can see in the NLS sequence RRMKWKK of PDX-1. This motif is sufficient for the nuclear import of PDX-1.<ref>PMID : 10567702</ref> | ||
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In order to regulate all of these genes, PDX1 interacts with different cofactors. | In order to regulate all of these genes, PDX1 interacts with different cofactors. | ||
In pancreatic δ-cells, PDX-1 interacts with PBX1 and PREP1 corresponding respectively to PBC and MEIS proteins. These proteins belong to the three amino acids loop extension (TALE) family of homeodomains. By interacting with these proteins, PDX-1 can regulate the somatostatin promoter. Interaction with the TALE proteins is mediated through a conserved pentapeptide motif, FPWMK, located at the 10 residues of the N-terminal of the homeodomain. | In pancreatic δ-cells, PDX-1 interacts with PBX1 and PREP1 corresponding respectively to PBC and MEIS proteins. These proteins belong to the three amino acids loop extension (TALE) family of homeodomains. By interacting with these proteins, PDX-1 can regulate the somatostatin promoter. Interaction with the TALE proteins is mediated through a conserved pentapeptide motif, FPWMK, located at the 10 residues of the N-terminal of the homeodomain. <ref>PMID : 11279116</ref> | ||
In neural cells, PDX-1 utilizes a different binding site on the somatostatin promoter than in δ-cells, suggesting a distinct protein complex. PDX-1 interacts also with the basic helix-loop-helix (bHLH) factor E47/NeuroD. | In neural cells, PDX-1 utilizes a different binding site on the somatostatin promoter than in δ-cells, suggesting a distinct protein complex. PDX-1 interacts also with the basic helix-loop-helix (bHLH) factor E47/NeuroD. | ||
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Diabete is a metabolic disorder characterized by a hyperglycemia resulting from defects in insulin secretion or insulin action in function of the type of the diabetes (type I or II). | Diabete is a metabolic disorder characterized by a hyperglycemia resulting from defects in insulin secretion or insulin action in function of the type of the diabetes (type I or II). <ref>PMID : 11834421</ref> | ||
Five different proteins with functional defects, cause a form of diabetes termed MODY ( included in type II diabetes). Those include the enzyme GK and four transcription factors, including PDX-1 (MODY-4). | Five different proteins with functional defects, cause a form of diabetes termed MODY ( included in type II diabetes). Those include the enzyme GK and four transcription factors, including PDX-1 (MODY-4). | ||
Mutations of PDX-1 have also effects on the development of the pancreas and on the function of insulin-secreting cells. | Mutations of PDX-1 have also effects on the development of the pancreas and on the function of insulin-secreting cells. | ||
It could also be a pharmacological target for beta-cell defects in Type II diabetes, since it has a role as regulator of islet of Langerhans stem cell activity. | It could also be a pharmacological target for beta-cell defects in Type II diabetes, since it has a role as regulator of islet of Langerhans stem cell activity. | ||
== References == | |||
<references/> | |||
