Topic
SIAH2
About: SIAH2 is a research topic. Over the lifetime, 100 publications have been published within this topic receiving 4553 citations. The topic is also known as: hSiah2 & siah E3 ubiquitin protein ligase 2.
Papers published on a yearly basis
Papers
TL;DR: In this article, Siah-1 interacts with the carboxyl terminus of APC and promotes degradation of β-catenin in mammalian cells, and the ability of Siah1 to downregulate β-Catenin signaling was also demonstrated by hypodorsalization of Xenopus embryos.
448 citations
TL;DR: It is demonstrated that the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia, uncovering oxygen availability as a microenvironment signal for the hippo pathway.
Abstract: Wu and colleagues report that under hypoxic conditions the LATS2 kinase is targeted for degradation by the SIAH2 ubiquitin ligase, leading to inhibition of the Hippo kinase cascade and activation of YAP, which promotes tumour growth.
258 citations
TL;DR: Through modulating Fis1/Drp1 complex availability, Siah2 is identified as a key regulator of hypoxia-induced mitochondrial fission and its physiological significance in ischemic injury and nematode life span.
244 citations
TL;DR: It is demonstrated that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells, and that DNA damage triggers disruption of the HIPK 2–Siah- 1 complex, resulting in HipK2 stabilization and activation.
Abstract: The tumour suppressor HIPK2 is an important regulator of cell death induced by DNA damage, but how its activity is regulated remains largely unclear. Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. During recovery from sublethal DNA damage, HIPK2, which is stabilized on DNA damage, is degraded through a Siah-1-dependent, p53-controlled pathway. Downregulation of Siah-1 inhibits HIPK2 degradation and recovery from damage, driving the cells into apoptosis. We have also demonstrated that DNA damage triggers disruption of the HIPK2–Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2–Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19. Our results provide a molecular framework for HIPK2 regulation in unstressed and damaged cells.
189 citations
TL;DR: This review summarizes the current understanding of Siah2 regulation and function with emphasis on hypoxia and tumorigenesis and indicates an important function for Siah1 in tumor development and progression based on pancreatic cancer, mammary tumor, and melanoma mouse models.
Abstract: Growing evidence indicates that ubiquitin ligases play a critical role in the hypoxia response. Among them, Siah2, a RING finger ligase, is an important regulator of pathways activated under hypoxia. Siah2 regulates prolyl hydroxylases PHD3 and 1 under oxygen concentration of 2% to 5%, thereby allowing accumulation of hypoxia-inducible factor (HIF)-1α, a master regulator of the hypoxia response within the range of physiological normoxic to mild hypoxic conditions. Growing evidence also indicates an important function for Siah2 in tumor development and progression based on pancreatic cancer, mammary tumor, and melanoma mouse models. This review summarizes our current understanding of Siah2 regulation and function with emphasis on hypoxia and tumorigenesis.
132 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2022 | 1 |
| 2021 | 3 |
| 2020 | 6 |
| 2019 | 3 |
| 2018 | 5 |
| 2017 | 10 |