Year: 2017
Type: editorial
Abstract: The cellular hypoxic response contributes to cell transformation and tumor progression. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor that mediates transcription of genes whose products are essential for cellular adaptation to hypoxia. The activity of HIF-1 is largely regulated by the abundance of its alpha subunit (HIF-1α), which is primarily regulated by an oxygen-dependent and ubiquitin/proteasome-mediated degradation process. The HIF-1α protein level is also regulated by protein kinases through phosphorylation. Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase with a tumor suppressive function. Plk3 phosphorylates and destabilizes HIF-1α. Plk3 also phosphorylates and stabilizes PTEN, a known regulator of HIF-1α stability via the PI3K pathway. Our latest study showed that the Plk3 protein is suppressed by hypoxia or nickel treatment via the ubiquitin/proteasome system. We discovered that Seven in Absentia Homologue 2 (SIAH2) is the E3 ubiquitin ligase of Plk3 and that Plk3 in turn destabilizes SIAH2. Given the role of SIAH2 in promoting stability of HIF-1α, our work reveals a novel mutual regulatory mechanism between Plk3 and SIAH2, which may function to fine-tune the cellular hypoxic response. Here we discuss the role of Plk3 in the hypoxic response and tumorigenesis in light of these latest findings.
Source: Cell Cycle
Institutions: New York Medical College, NYU Langone Health
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: G2217173815, G9000039094
OpenAlex ID: W2751374142