Sandbox Reserved 168

SKI proteinSKI protein

spinqualitylabelsall models Crystal Structure of human SKI, PDB ID: 1SBX Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

This Sandbox is Reserved from March 9, 2011, through May 30, 2011 for use by the course Biochemistry at Reinhardt University, Waleska, USA, taught by Irma Santoro. This reservation includes Sandbox Reserved 162 through Sandbox Reserved 168.

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BackgroundBackground

The SKI protein was first identified as an oncoprotein. An oncoprotein is one that has the potential to cause abnormal cellular proliferation if mutated or if expressed in quantitative amounts. Although, for a time the method by which the SKI protein acquired such capabilities was unknown, it was recently discovered that SKI interacts with smad after stimulation by TGF-beta. TGF-beta are proteins directly associated with proliferation and cellular differentiation, while smads are transcription factors that transduce transforming growth factor-betar(TGF-beta) members to activate transcription. SKI blocks the activation of transcription witht eh smad complexes which makes the cells resistant to the inhibitory reactions of normal growth induced by TGF-beta. Note that the stimulation of TGF-beta may cause the rapid degradation of SKI. However, after a relatively brief amount of time its expression is strongly induced. .

StructureStructure

This protein is made up of 728 amino acids. The SKI protein maintains several domains that include the amino-terminus, a proline rich area, helix-loop-helix motifs, a cysteine/histidine-rich area, a region of basic amino acids and finally a leucine zipper-like domain.

FunctionFunction

SKI, as mentioned before is an oncoprotein that represses TGF-beta and nuclear receptor signaling. It is involved in the regulation of cellular transformation and differentiation. The SKI protein has been associated with tumors at large levels of cellular concentrations and it has been shown to interfere with normal cellular functioning. It was recently discovred that SKI plays a role not only inside the nucleus but also outside of the nucleus in the cytoplasm.

Clinical ApplicationsClinical Applications

SKI has been linked to various types of cancer such as melanoma, esophageal cell carcinoma, cervical cancer and the process of tumor progresssion. The SKI oncoprotein has been demonstrated to assist tyrosine kinases to cause leukemia, recently it has been demonstrated that the protein also plays a regulatory role in several signal transduction pathways that are frequent targets for mutagenesis in human tumors.