Switches.ELM

Switch #:

SWTI000517

Switch type:
Binary

Description:
Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life.

Participants:
(1) Cellular tumor antigen p53 (TP53)
(2) E3 ubiquitin-protein ligase Mdm2 (MDM2)

Interactions

Interaction #1 TP53 - MDM2

Interfaces
(1) DEG_MDM2_1 motif (₁₉FSDLWKLL₂₆) in Cellular tumor antigen p53 (TP53)
(2) SWIB/MDM2 domain_(27-102) in E3 ubiquitin-protein ligase Mdm2 (MDM2)

Interaction Regulation
Alternative promoter usage and alternative splicing Abrogation of the Cellular tumor antigen p53 (TP53) DEG_MDM2_1 motif - E3 ubiquitin-protein ligase Mdm2 (MDM2) SWIB/MDM2 domain interaction

Context

Switch localisation
ELM curated: nucleus, cytosol

Inferred: nucleolus, cytosol

Switch cell cycle phase
Curated: DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest

Switch pathways
Curated: p53 signaling pathway, Cell cycle, p53-Dependent G1/S DNA damage checkpoint

Inferred: PI3K-Akt signaling pathway

References

(1) DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53.
Courtois et al. Oncogene (2002)

(2) p53 isoforms - a conspiracy to kidnap p53 tumor suppressor activity?
Marcel et al. Cell. Mol. Life Sci. (2009)