Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNF4, a poly-SUMO-specific E3 ubiquitin ligase, is associated with protein degradation, DNA damage repair and tumour progression. However, the effect of RNF4 in cardiomyocytes remains to be explored. Here, we identified the alteration of RNF4 from ischaemic hearts and oxidative stress-induced apoptotic cardiomyocytes. Upon myocardial infarction (MI) or H₂ O₂ /ATO treatment, RNF4 increased rapidly and then decreased gradually. PML SUMOylation and PML nuclear body (PML-NB) formation first enhanced and then degraded upon oxidative stress. Reactive oxygen species (ROS) inhibitor was able to attenuate the elevation of RNF4 expression and PML SUMOylation. PML overexpression and RNF4 knockdown by small interfering RNA (siRNA) enhanced PML SUMOylation, promoted p53 recruitment and activation and exacerbated H₂ O₂ /ATO-induced cardiomyocyte apoptosis which could be partially reversed by knockdown of p53. In vivo, knockdown of endogenous RNF4 via in vivo adeno-associated virus infection deteriorated post-MI structure remodelling including more extensive interstitial fibrosis and severely fractured and disordered structure. Furthermore, knockdown of RNF4 worsened ischaemia-induced cardiac dysfunction of MI models. Our results reveal a novel myocardial apoptosis regulation model that is composed of RNF4, PML and p53. The modulation of these proteins may provide a new approach to tackling cardiac ischaemia.
...
PMID:Knockdown of endogenous RNF4 exacerbates ischaemia-induced cardiomyocyte apoptosis in mice. 3272 82

The stability and activity of the p53 tumor suppressor protein are tightly regulated by various posttranslational modifications, including SUMOylation. p53 can be modified by both SUMO1 and SUMO2, although how SUMOylation regulates p53 activity is still obscure. Whether p53 activity is directly regulated by deSUMOylation is also unclear. Here, we show that SENP1, a SUMO-specific protease implicated in pro-oncogenic roles, is a p53 deSUMOylating enzyme. SENP1 interacts with p53 and deSUMOylates p53 in cells and in vitro. Knockdown of SENP1 markedly induced p53 transactivation activity. We further show that SENP1 depletion synergizes with DNA damage-inducing agent etoposide to induce p53 activation and the expression of p21, leading to synergistic growth inhibition of cancer cells. Our results reveal that SENP1 is a critical p53 deSUMOylating enzyme and a promising therapeutic target in wild-type p53 containing cancer cells.
...
PMID:The SUMO-specific protease SENP1 deSUMOylates p53 and regulates its activity. 3278 21

Liver regeneration represents an outstanding tool to study not only proliferation, but also other important processes such as inflammation, regenerative response or stem cell biology. Several novel genes have been identified as being involved in the proliferation of residual hepatocytes. One of them, HOPS/TMUB1, is proving to be a significant player in the control of proliferation, both contributing to genomic stability and as a partner of essential molecules. HOPS is an ubiquitin-like protein, shuttling from nucleus to cytoplasm, and it is engaged in a number of biological and physiopathological functions. HOPS overexpression in tumour cell lines strongly reduces proliferation, arresting cell cycle in G₀ /G₁ . HOPS is involved in centrosome assembly and maintenance, and its knockdown causes genomic instability. Moreover, a direct interaction of HOPS with nucleophosmin (NPM) and p19^Arf has been established, resulting in proper control of p19^Arf stability and localization. These data indicate that HOPS acts as a functional bridge in the interaction between NPM and p19^Arf , providing new mechanistic insight into how NPM and p19^Arf will oppose cell proliferation. HOPS exerts a control in p53 stability, directing p53 mitochondrial apoptosis and cytoplasmic localization. HOPS plays a direct role as novel post-translational modifier of p53, much like SUMO or NEDD. HOPS is overexpressed in a high number of human tumours in patients affected by large intestinal, CNS, liver and oesophageal tumours. This review highlights HOPS involvement in distinct cellular functions, establishing its role as a key player in cell biology and pathology in a broader context.
...
PMID:The Ins and Outs of HOPS/TMUB1 in biology and pathology. 3286 Apr 79


<< Previous 1 2 3 4 5 6 7 8 9 10

---