Supplementary Figure 1 from p53–Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT

Yang-Hartwich, Yang; Tedja, Roslyn; Roberts, Cai M.; Goodner-Bingham, Jamie; Cardenas, Carlos; Gurea, Marta; Sumi, Natalia J.; Alvero, Ayesha B.; Glackin, Carlotta A.; Mor, Gil

doi:10.1158/1541-7786.22515390.v1

15417786mcr180238-sup-198187_2_supp_4907977_pc6ckr.pdf (39.1 kB)

Supplementary Figure 1 from p53–Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT

journal contribution

posted on 2023-04-03, 17:21 authored by Yang Yang-Hartwich, Roslyn Tedja, Cai M. Roberts, Jamie Goodner-Bingham, Carlos Cardenas, Marta Gurea, Natalia J. Sumi, Ayesha B. Alvero, Carlotta A. Glackin, Gil Mor

The protein levels of Twist1 (A) and p53 (B) in tumor samples. Protein levels were determined by the quantification of western blot band intensity comparing to GAPDH bands as loading control.

Funding

NCI

NIH

Office of the Assistant Secretary for Health

History

ARTICLE ABSTRACT

Epithelial–mesenchymal transition (EMT) is a critical process involved in cancer metastasis and chemoresistance. Twist1 is a key EMT-inducing transcription factor, which is upregulated in multiple types of cancers and has been shown to promote tumor cell invasiveness and support tumor progression. Conversely, p53 is a tumor suppressor gene that is frequently mutated in cancers. This study demonstrates the ability of wild-type (WT) p53 to promote the degradation of Twist1 protein. By forming a complex with Twist1 and the E3 ligase Pirh2, WT p53 promotes the ubiquitination and proteasomal degradation of Twist1, thus inhibiting EMT and maintaining the epithelial phenotype. The ability of p53 to induce Twist1 degradation is abrogated when p53 is mutated. Consequently, the loss of p53-induced Twist1 degradation leads to EMT and the acquisition of a more invasive cancer phenotype.Implication: These data provide new insight into the metastatic process at the molecular level and suggest a signaling pathway that can potentially be used to develop new prognostic markers and therapeutic targets to curtail cancer progression.