ZBTB2 links p53-deficiency to HIF-1-mediated hypoxia signaling to promote cancer aggressiveness

ABSTRACT: Aberrant activation of the hypoxia-inducible transcription factor HIF-1 and dysfunction of the tumor suppressor p53 have been reported to induce malignant phenotypes and therapy-resistance of cancers. However, their mechanistic and functional relationship remains largely unknown. Here, we reveal a mechanism by which p53 deficiency triggers the activation of HIF-1-dependent hypoxia signaling and identify zinc finger and BTB domain-containing protein 2 (ZBTB2) as an important mediator. ZBTB2 forms homodimers via its N-terminus region and increases the transactivation activity of HIF-1 only when functional p53 is absent. The ZBTB2 homodimer facilitates invasion, distant metastasis, and growth of p53-deficient, but not p53-proficient, cancers. The intratumoral expression levels of ZBTB2 are as

SUBMITTER: Dr. Sho Koyasu 

PROVIDER: S-SCDT-10_15252-EMBR_202154042 | biostudies-other |

REPOSITORIES: biostudies-other