What is the link between p14ARF and p53?
What is the link between p14ARF and p53?
p14ARF inhibits Mdm2-dependent p53 degradation, through Mdm2-p14ARF complex formation (Zhang et al., 1998). Thus, in response to genotoxic stress induced by gamma-radiation, p14ARF binds directly to Mdm2, leading to an inhibition of Mdm2-mediated p53 ubiquitination and degradation, which increases p53 levels.
Is p14ARF a tumor suppressor?
P14ARF is a tumor suppressor encoded by the CDKN2a locus that is frequently inactivated in human tumors. P14ARF protein quenches oncogene stimuli by inhibiting cell cycle progression and inducing apoptosis. P14ARF functions can be played through interactions with several proteins.
What kind of protein is p14ARF?
p14ARF (p19Arf in mice) is a 14kDa (19 kDa) protein predominantly localized in the nucleolus. It blocks the cell cycle in both G1 and G2 phases and inhibits the growth of incipient cancer cells by indirectly activating p53. It also inhibits ribosomal RNA processing and interacts with topoisomerase I.
What is ARF in Mdm2?
Abstract. The INK4a-ARF locus encodes two unrelated proteins that both function in tumor suppression. p16 INK4a binds to and inhibits the activity of CDK4 and CDK6, and ARF arrests the cell cycle in a p53-dependent manner. We show here that ARF binds to MDM2 and promotes the rapid degradation of MDM2.
What does MDM2 stand for?
Mouse double minute 2 homolog
Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by the MDM2 gene. Mdm2 is an important negative regulator of the p53 tumor suppressor.
What are INK4 factors?
INK4 is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, p19INK4d) are inhibitors of CDK4 (hence their name INhibitors of CDK4), and of CDK6. The other family of CKIs, CIP/KIP proteins are capable of inhibiting all CDKs.
What does ARF gene do?
Definition. ARF (alternative reading frame) is a tumor suppressor protein that accumulates in the nucleolus in response to aberrant oncogenic/hyperproliferative signals and induces cell cycle arrest in G1/S or G2/M transition and apoptosis.
Does ARF inhibit MDM2?
ARF binds to MDM2 in the CAD and inhibits MDM2-mediated p53 ubiquitination and degradation (Weber et al., 2000b; Bothner et al., 2001).
What do ARF proteins do?
The ADP-ribosylation factor (ARF) small GTPases regulate vesicular traffic and organelle structure by recruiting coat proteins, regulating phospholipid metabolism and modulating the structure of actin at membrane surfaces.
Where is MDM2 found?
In humans, the MDM2 gene (also known as HDM2) is located on chromosome 12q14. 3-q15 and most frequently expresses a 491 amino acid residue protein. MDM2 is amplified at an overall frequency of 7% in human cancers and at a higher frequency within soft tissue sarcomas, osteosarcomas, and esophageal carcinomas (4, 5).
What is the p21 gene?
Cyclin-dependent kinase inhibitor 1, also known as CDK-interacting protein 1, or more simply as p21, is a cell cycle inhibitor that promotes both CDK/cyclin inhibition as well as cell cycle arrest during the G1/S phase. In humans, p21 is encoded by the CDKN1A gene on chromosome six.
What is INK4 gene?
INK4 proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis. INK4 proteins are highly similar in terms of structure and function, with up to 85% amino acid similarity. They contain multiple ankyrin repeats.