The E2F4/p130 repressor complex cooperates with oncogenic Np73 to promote cell survival

ABSTRACT: Tumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the Np73 isoform is notoriously associated with poor prognosis in cancer. Here, we have performed proteomics analysis of Np73 using as a cellular model human papillomavirus type 38-transformed keratinocytes (38HK) that express high levels of this isoform. We find that Np73 associates with the E2F4/p130 repressor complex through a direct interaction with E2F4. Remarkably, this interaction is favored by the N-terminal truncation of p73 characteristic of Np73 isoforms and is independent of the C-terminal splicing status. We show that the Np73-E2F4/p130 complex is recruited to the promoters of specific genes, thereby enforcing inhibition of their expression both in 38HK and in cancer-derived cell lines. Consistently, silencing of E2F4 in 38HK and in cancer cells resulted in induction of senescence. In conclusion, we have identified and characterized a novel transcriptional regulatory complex that exerts pro-proliferative functions in transformed cells

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Papillary Renal Cell Carcinoma

SUBMITTER: Luc Negroni  

LAB HEAD: Katia Zanier

PROVIDER: PXD022947 | Pride | 2023-02-28

REPOSITORIES: Pride