NEDD4 Antibodies

E3 ubiquitin-protein ligase NEDD4 (NEDD4)

Specifically ubiquitinates'Lys-63' in target proteins (PubMed:23644597). Involved in the pathway resulting in the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity.

Monoubiquitinates IGF1R at multiple sites, thus resulting in receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, resulting in receptor internalization and degradation in lysosomes.

Gene Information

Human
Gene Name:	NEDD4
Uniprot:	P46934
Entrez:	4734

Family

Belongs to:
No superfamily

Alternative Names

Cell proliferation-inducing gene 53 protein; E3 ubiquitin-protein ligase NEDD4; EC 6.3.2; EC 6.3.2.-; KIAA0093NEDD4-1MGC176705; NEDD4; NEDD-4; Neural precursor cell expressed developmentally down-regulated protein 4; neural precursor cell expressed, developmentally down-regulated 4; receptor-potentiating factor 1; RPF1

Molecular Weight

Mass (kDA):
149.114 kDA

Genomic Context

Human
Location:	15q21.3
Sequence:	15; NC_000015.10 (55826917..55993612, complement)

Subcellular Localizations

Cytoplasm. Cell membrane; Peripheral membrane protein. Recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity). May be recruited to exosomes by NDFIP1.

Diseases

• Hypertensive Disease
• Liddle Syndrome
• Malignant Neoplasms
• Neoplasms
• Hiv Infections
• Atrophy
• Sarcoma
• Immunologic Deficiency Syndromes
• Pseudohypoaldosteronism
• Nervousness
• Cell Transformation, Neoplastic

• Muscular Atrophy
• Leukemia
• Cystic Fibrosis
• Fibrosis
• Essential Hypertension
• Vesicular Stomatitis

Interacting Proteins

• EGFR
• FGFR1
• GABARAP
• GABARAPL1
• GABARAPL2

• LITAF
• PTEN
• RNF11
• SCNN1B
• SMURF2

Pathways

• Transport
• Endocytosis
• Localization
• Cell Growth
• Muscle Atrophy
• Pathogenesis
• Protein Ubiquitination
• Cell Proliferation
• Proteolysis
• Cell Cycle
• Rna Interference
• Cell Adhesion
• Translation

• Induction Of Apoptosis
• Conjugation
• Angiogenesis
• Skeletal Muscle Atrophy
• Clathrin-mediated Endocytosis
• Cell Activation
• T Cell Activation

PTMs

• Ubiquitination
• Phosphorylation
• Cleavage
• Sumoylation
• Nitrosylation
• Isgylation

• Dephosphorylation
• Acylation
• Biotinylation
• Glycosylation
• Methylation
• Palmitoylation

• Myristoylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/NEDD4

Boster Bio: Best Uses of the NEDD4 Marker

The NEDD4 marker is a multi-faceted gene that is found in a variety of cells. Boster scientists can submit samples, species or applications for credit for product. This applies to scientists from all over the globe. The Boster Bio Best Uses for The NEDD4 Marker website gives information about many aspects of the gene, as well as its potential uses.

The prognosis for CN AML is poor for NEDD4L expression.

This study examined whether NEDD4L expression in CN-AML may be associated with a low prognosis. We used fresh frozen human GC tissue as a template and extracted mRNA with the TRIzol Reagent (Invitrogen). The ReverTra Ace qPCR Reagent was used to conduct QPCR. Reverse transcription-PCR was employed to determine the levels of mRNA for NEDD4L HIF-1a, CASP-3 and NEDD4L using specific primers (NEDD4L and CASP-3).

Genomicscape is an online tool that allows researchers to examine 78 CN/AML groups. A low NEDD4L expression was significantly associated with an unfavorable prognosis. Additionally, patients with low levels of NEDD4L showed more frequent genetic mutations (NFM1 TET2, U2AF1 FLT3, and so on.) Patients with low levels NEDD4L expression had less favorable outcomes than those with higher levels.

The NEDD4 family includes the gene NEDD4. It has an distinct modular domain structure. They have a phospholipid binding site as well as four WW domains, and an inhibitor of the Ca2+ channel. Additionally, they regulate the PI3K/AKT signaling pathway. Although NEDD4L is associated with a poor prognosis in CN-AML, there is no consensus on whether this gene plays an impact on the development of the disease.

Furthermore, NEDD4L is negatively associated with miR-10a, a gene which is directly linked with NEDD4L. A recently discovered miR-10a also linked to NEDD4L plays an oncogenic part. However, this connection has not yet been confirmed through luciferase tests.

NEDD4L is often associated to poor prognosis for a variety of cancers including CN-AML. In addition to gastric cancer It has also been associated with a poor prognosis according to research published in the journal Med Oncol. In conclusion, NEDD4L might play a role in tumor suppression in the development of AML.

NEDD4L and HIF-1a are two genes associated with GC prognosis. In addition, HIF-1a and HIF-2a are associated with a poor prognosis in CN AML. Furthermore, HIF-1a and NEDD4L expression is associated with the GC stage.

In this study the expression of NEDD4L and HIF-1a was found to be associated with poor prognosis in a small subset of patients with CN-AML. Prolonged prognosis was related to high levels of HIF-1a and NEDD4L and HIF-1a. HIF-1a was associated with poor response to treatment and a higher chance of relapse.

However, only a few studies confirm that NEDD4L high expression is associated with poor prognosis. It isn't clear whether this connection is due genetic or other factors. It is a clear indicator of the need to conduct genetic tests for this disease. In the meantime, there is no reason why NEDD4L expression in CN-AML isn't associated with a poor prognosis.

NEDD4L is an element of the Cullin family of RING Ubiquitin Ligases. They recruit a variety a adaptor and RING finger proteins to the cell membrane. CUL4A, CUL2 and CUL2 cullins for instance, recruit F-box protein. DCAF proteins bind SOCS and FBXW8 to their substrates. Despite being a highly functional gene, NEDD4L in CN AML is linked with a poor prognosis.

NEDD4L expression is correlated with HIF-1alpha levels in gastric cancer

Recent research has shown that NEDD4L levels are correlated with HIF-1alpha. We also discovered that NEDD4L expression is linked to one subset of microRNAs, referred to as miR-10a. We discovered that NEDD4L is also pro-apoptotic, as well as anti-proliferative. These findings support the hypothesis of NEDD4L controlling the expression of HIF-1alpha during gastric cancer.

We combined AceQ qPCR SYBR Green Master Mix to detect mRNA from cancerous gastric cells. CASP3 and CASP8 expressions were also significantly higher than those of control cells. We also observed an increase in phospho IkBa levels in cells with NEDD4LKD. This suggests that the low NEDD4L expression causes the degradation of proteins through proteasome.

We measured autophagic fluxes within MM cells using standard assays. We observed that NEDD4LKD MM cells had a significantly lower ratio of LC3A/B/II and LC3A/B/I suggesting that NEDD4L blocks the process. These results suggest that NEDD4L is a key player in regulating the HIF-1alpha levels in gastric cancer.

Ndrg1 is a tumor suppressor. Ndrg1 mice lacking it were diagnosed with progressive demyelination syndrome a mouse model of colorectal cancer. This study also uncovers an entirely new molecular target known as Cap43/NDRG1/Drg-1. If we can discover the means to activate this gene in gastric cancer, we could be on the way to creating new medications for the treatment of cancer.

The hypoxia-inducible HIF-1alpha protein can affect the expression of NDRG gene genes. Additionally, HIF-1a blocks the expression of the hypoxic cells by directly activating the NDRG genes. They regulate the expression of key factors in hypoxic conditions. For instance, HIF-1a is a blocker of the phosphorylation of b-catenin, which is essential for hypoxic cells to adjust.

ARP-1 MM cells were treated for 24 hours with HCQ (10 mM). In vitro NEDD4L knockdown reduced the cells' ability to detect Bor. However, the results in vivo are also encouraging. The expression of NEDD4L is positively associated with the levels of HIF-1alpha within gastric cancer.

This study shows that NEDD4L knockdown can reduce tumor size by about 80percent. However, this knockdown has not been confirmed in humans. This is a major obstacle in the treatment of gastric cancer. From a clinical perspective it is vital to have effective targets. These findings could eventually provide better treatments for gastric cancer.

Many studies indicate that NEDD4L expression is correlated to the level of HIF-1alpha levels in gastric cancer. However, more work is needed to establish the specific mechanism through which NEDD4L stimulates HIF-1alpha's expression. NEDD4L is an E3 ubiquitin ligase cullin-RING, an multi-subunit RING Ligase that recruits four essential subunits. The subunits comprise scaffolds, which connect the adaptor subunit and RING fingers and provides an upper platform for the RING.

UB-Flag expression is correlated to NEDD4L expression in leukemic cell lines

NEDD4L expression results in HIV-1 viral particle (VLP), particles to be released. HIV-1 gagDPTAP was determined in cells that were transfected with empty expression vectors or NEDD4LWT. HIV-1 GagDPTAP titers were measured by measuring the viral particle titer as well as Gag protein from the cell. Additionally the NEDD4L-like E3 Ubiquitin ligases blocked the release of viral particles and the expression of UB-Flag in cellular leukemia.

NEDD4L plays a role in autophagy, as well as mitochondrial metabolism. It hinders autophagy by reducing the levels of ULK1 and ASCT2. The NEDD4L inhibitor also reduces pancreatic cancer cell growth and survival. Furthermore, knockdown of NEDD4L causes a decrease in the growth of pancreatic cancer cells as well as an increase in the oxygen consumption rate (OCR).

NEDD4L-HA overexpression prevented A375 cell proliferation and migration. The ubiquitinated proteins resulting from this were detected by immunoprecipitation assays. In addition, ubiquitination through NEDD4L of SP1 was correlated to UB-Flag expressions in leukemic cells lines. The co-expression of NEDD4L with UB-Flag was demonstrated using fluorescence-based co-localization experiments.

NEDD4L is required for efficient cell cytokinesis in HeLa cell lines. Multinuclear cells can be identified by staining microtubules by immunofluorescence using Sytox green. Yellow arrowheads highlight visible midbodies. Microscopically counting mononucleated cells showed their peak volume.

NEDD4L targets SphK2 for degradation by the ubiquitin-proteasomal pathway. This blocks AKT/bcatenin signaling which is essential in the fight against tumors. It also blocks the proliferation of cancerous glioma cells, and encourages apoptosis.

The mice were killed during the study. The tumors were photographed and weighted. In some studies, the mice received Ctrl-R or JP1 in order to decrease the growth of tumors. The mice were killed 40 days after the day the tumors began to grow. This study suggests that NEDD4L could be a potential therapeutic target for treating leukemia or glioma.

Moreover, NEDD4L has a correlation with SP1 ubiquitination suggesting that it could be a therapeutic target for Melanoma. It reduces metastasis in mice and also has anti-cancer properties in melanoma. In vitro studies, NEDD4L induced the ubiquitin ligases SP1 and MEK1/2, while in vivo, it slowed the growth of leukemic cancer cells by decreasing the dose of DTIC.

The study was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University. The Second Affiliated Hospital of Anhui Medical University approved the animal experiment. The expression of UB-Flag and NEDD4L in leukemic cells were discovered to be related in peripheral blood that is normal and cancerous.