Preferred Label : Splicing Regulation Pathway;
NCIt related terms : Regulation of Splicing through Sam68;
Alternative definition : BIOCARTA: While transcriptional regulation is often viewed as the most prevalent way
extracellular signals act to regulate gene expression, post-transcriptional regulation
of splicing, RNA stability, and translation are also regulated by extracellular signals.
Sam68, a member of a family of RNA-binding proteins called STAR proteins, mediates
alternative splicing in response to extracellular signals, such as altered splicing
of CD44 in response to phorbol ester treatment of T cells. RNA binding and activity
of SAM68 is regulated by upstream signals through phosphorylation and modulating of
its interaction with other proteins, itself, and with RNA. Phorbol ester treatment
of T cells stimulates the ras/ Map kinase pathway, activating Erk and phosphorylation
of Sam68, inducing alternative splicing of CD44 and perhaps other cellular RNA targets.
Sam68 is localized in the nucleus to a specific substructure called the Sam68/SLM
Nuclear Bodies, colocalizing with splicing factors and helping to link signal transduction
with RNA processing. Sam68 has been suggested to play a role in a variety of pathways,
including insulin signaling and HIV gene expression, substituting for the activity
of viral Rev protein, and being regulated by arginine methylation as well as phosphorylation.
In addition to the role of Sam68 regulating posttranscriptional gene expression, Sam68
also interacts with transcription factors such as CBP and appears to regulate gene
expression. Sam68 also appears to play a role in cell cycle progression through influencing
RNA processing. During mitosis SAM68 is tyrosine phosphorylated and associated with
Src. The interaction of Sam68 with RNA is repressed by this phosphorylation, whereas
interaction of Sam68 with Ras-GAP is stimulated by phosphorylation. Sam68 appears
to be downregulated in tumors and transformed cells and its expression is reduced
during mitosis, suggesting it inhibits proliferation. The RNA binding domain in Sam68,
called a KH domain, is absent in a splice isoform that is expressed in cells that
display contact inhibition of cellular growth. Sam68 with the KH domain appears in
some settings to stimulate the G1/S transition, while blocking mitosis in some reports.
(This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_sam68Pathway;
Origin ID : C39228;
UMLS CUI : C1519479;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
