scholarly journals Insights Into the Biological Role of NEDD4L E3 Ubiquitin Ligase in Human Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Shangdan Xie ◽  
Lu Xia ◽  
Yizuo Song ◽  
Hejing Liu ◽  
Zhi-wei Wang ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Therapeutic Strategy ◽  
Potential Role ◽  
E3 Ubiquitin Ligase ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Cancer Types ◽  
Clinical Drugs

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is an E3 ubiquitin ligase that has been reported to participate in multiple cellular procedures by regulating of substrate ubiquitination and subsequent protein degradation. A great amount of evidence has demonstrated that NEDD4L mainly functions as a tumor suppressor in most cancer types, while it also acts as an oncogene in a few cancers. In this review, we summarize the potential role of NEDD4L in carcinogenesis and the related underlying molecular mechanism to improve our understanding of its functions in the tumorigenesis of human malignancies. Developing clinical drugs targeting NEDD4L could be a potential therapeutic strategy for cancer therapy in the future.

scholarly journals The Role of Mcl-1 in Embryonic Neural Precursor Cell Apoptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Robert T. Flemmer ◽  
Sarah P. Connolly ◽  
Brittany A. Geizer ◽  
Joseph T. Opferman ◽  
Jacqueline L. Vanderluit
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Precursor Cell ◽  
Embryonic Lethality ◽  
Conditional Knockout ◽  
Neural Precursor ◽  
Null Mouse ◽  
Neural Precursor Cell ◽  
Thoracic Spinal Cord

Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 protein, regulates neural precursor cell (NPC) survival in both the developing and adult mammalian nervous system. It is unclear when during the neurogenic period Mcl-1 becomes necessary for NPC survival and whether Bax is the sole pro-apoptotic target of Mcl-1. To address these questions, we used the nervous system-specific Nestin-Cre Mcl-1 conditional knockout mouse line (Mcl-1 CKO) to assess the anti-apoptotic role of Mcl-1 in developmental neurogenesis. Loss of Mcl-1 resulted in a wave of apoptosis beginning in the brainstem and cervical spinal cord at embryonic day 9.5 (E9.5) and in the forebrain at E10.5. Apoptosis was first observed ventrally in each region and spread dorsally over time. Within the spinal cord, apoptosis also spread in a rostral to caudal direction following the path of differentiation. Breeding the Mcl-1 CKO mouse with the Bax null mouse rescued the majority of NPC from apoptosis except in the dorsomedial brainstem and ventral thoracic spinal cord where only 50% were rescued. This demonstrates that Mcl-1 promotes NPC survival primarily by inhibiting the activation of Bax, but that Bax is not the sole pro-apoptotic target of Mcl-1 during embryonic neurogenesis. Interestingly, although co-deletion of Bax rescued the majority of NPC apoptosis, it resulted in embryonic lethality at E13, whereas conditional deletion of both Mcl-1 and Bax rescued embryonic lethality. In summary, this study demonstrates the widespread dependency on Mcl-1 during nervous system development.

PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle

2016 ◽  
Vol 473 (3) ◽  
pp. 267-276 ◽  
Author(s):  
Robert D'Cruz ◽  
Pamela J. Plant ◽  
Lesley A. Pablo ◽  
Shouzhe Lin ◽  
Joshua Chackowicz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ubiquitin Ligase ◽  
Muscle Wasting ◽  
Precursor Cell ◽  
Skeletal Muscle Atrophy ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Ww Domains ◽  
Novel Target ◽  
Py Motif

Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) mediates skeletal muscle atrophy. We identify PDLIM7 as a novel Nedd4-1 substrate, binding Nedd4-1 WW domains via its PY motif and co-localizing with Nedd4-1 in myotubes. The interaction results in PDLIM7 ubiquitination and may underlie Nedd4-1-mediated muscle wasting.

Serum- and Glucocorticoid-Regulated Kinase 1 Regulates Ubiquitin Ligase Neural Precursor Cell-Expressed, Developmentally Down-Regulated Protein 4-2 by Inducing Interaction with 14-3-3

2005 ◽  
Vol 19 (12) ◽  
pp. 3073-3084 ◽  
Author(s):  
Vivek Bhalla ◽  
Dorothée Daidié ◽  
Hongyan Li ◽  
Alan C. Pao ◽  
Lila P. LaGrange ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell

scholarly journals The inositol phosphatase MTMR4 is a novel target of the ubiquitin ligase Nedd4

2009 ◽  
Vol 419 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Pamela J. Plant ◽  
Judy Correa ◽  
Neil Goldenberg ◽  
James Bain ◽  
Jane Batt
Keyword(s):  
Ubiquitin Ligase ◽  
Biological Process ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Related Protein ◽  
Inositol Phosphatase ◽  
Late Endosomes ◽  
Muscle Breakdown ◽  
Novel Target

The inositol phosphatase, MTMR4 (myotubularin-related protein 4), was identified as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). hMTMR4 (human MTMR4) and Nedd4 co-immunoprecipitated and co-localized to late endosomes. The PY (Pro-Tyr) motif of hMTMR4 binds to WW (Trp-Trp) domains of hNedd4. MTMR4 expression was decreased in atrophying muscle, whereas Nedd4 expression was increased and hMTMR4 was ubiquitinated by hNedd4, suggesting that this novel interaction may underlie the biological process of muscle breakdown.

scholarly journals Regulation of cancer-related pathways by protein NEDDylation and strategies for the use of NEDD8 inhibitors in the clinic

2014 ◽  
Vol 22 (1) ◽  
pp. T55-T70 ◽  
Author(s):  
Naima Abidi ◽  
Dimitris P Xirodimas
Keyword(s):  
Therapeutic Intervention ◽  
Biological Process ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Post Translational Modification ◽  
Recent Advances

Post-translational modification of proteins with ubiquitin and ubiquitin-like molecules (UBLs) controls a vast if not every biological process in the cell. It is not surprising that deregulation in ubiquitin and UBL signalling has been implicated in the pathogenesis of many diseases and that these pathways are considered as major targets for therapeutic intervention. In this review, we summarise recent advances in our understanding of the role of the UBL neural precursor cell expressed developmentally downregulated-8 (NEDD8) in cancer-related processes and potential strategies for the use of NEDD8 inhibitors as chemotherapeutics.

scholarly journals Caenorhabditis elegans germline development requires brap-2

2018 ◽  
Author(s):  
Dayana R D'Amora ◽  
Queenie Hu ◽  
Monica Pizzardi ◽  
Terrance Kubiseski
Keyword(s):  
Ubiquitin Ligase ◽  
Brood Size ◽  
Potential Role ◽  
Chromosomal Abnormalities ◽  
E3 Ubiquitin Ligase ◽  
Retention Factor ◽  
Germline Development ◽  
C Elegans ◽  
Mammalian Tissues

Background. Mutations in C. elegans can produce visible and quantifiable defects in morphology, lifespan, and development. BRAP2/IMP (BRCA1-associated binding protein 2) has been characterized as an E3 ubiquitin ligase, a general cytoplasmic retention factor, a potential scaffold protein, and is found to be widely expressed throughout various mammalian tissues, most highly in testes. However, its role in the development or health of these tissues has not been addressed. Results. The focus of this study is to determine the role of BRAP-2 in C. elegans germline development. We determined that brap-2 mutants display defects in germline morphology and a reduction in brood size. We also found that chromosomal abnormalities and embryonic lethality are elevated in brap-2 mutants following DNA damage, suggesting a potential role for BRAP-2 in facilitating DNA repair. Conclusions. Our findings indicate that BRAP-2 is required for C. elegans germline health and identifies a novel role for BRAP-2 in germline development.

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