Preferred Label : Ribosomal Biogenesis Pathway;
NCIt related terms : Tumor Suppressor Arf Inhibits Ribosomal Biogenesis;
Alternative definition : BIOCARTA: Cyclin-dependent kinase inhibitor-2A (CDKN2A) goes by the colloquial designation
p16, which is sometimes referred to as p16(INK4). The alpha transcript of CDKN2A has
been shown to encode p16(INK4a), a recognized tumor suppressor that induces a G1 cell
cycle arrest by inhibiting the phosphorylation of the RB protein by the cyclin-dependent
kinases CDK4 and CDK6. The beta transcript of CDKN2A encodes p14(ARF). The predicted
132-amino acid p14(ARF) is shorter than the corresponding mouse protein, p19(ARF),
and the 2 proteins share only 50% identity. However, both proteins have the ability
to elicit a p53 response, manifest in the increased expression of both CDKN1A and
MDM2, and resulting in a distinctive cell cycle arrest in both the G1 and G2/M phases.
Two unrelated proteins encoded by the INK4A-ARF locus function in tumor suppression.
ARF binds to MDM2 and promotes the rapid degradation of MDM2. This interaction is
mediated by the E1-beta-encoded N-terminal domain of ARF and a C-terminal region of
MDM2. ARF-promoted MDM2 degradation is associated with MDM2 modification and concurrent
p53 stabilization and accumulation. The p19(Arf) tumor suppressor inhibits production
of ribosomal RNA, retarding processing of 47/45S and 32S precursors. These effects
correlate with but do not strictly depend upon inhibition of rRNA biosynthesis or
cell cycle arrest, are not mimicked by p53, and require neither p53 nor Mdm2. Arf
mutants lacking conserved amino acid residues 2-14 do not block rRNA synthesis and
processing or inhibit cell proliferation. Evolution may have linked a primordial nucleolar
Arf function to Mdm2 and p53, creating a more efficient checkpoint-signaling pathway
for coordinating ribosomal biogenesis and cell cycle progression. (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may be outdated - see the DesignNote.);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Definition might be outdated or inaccurate.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_arfPathway;
Origin ID : C38992;
UMLS CUI : C1514942;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
