scholarly journals The Role of Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 4.1- Mediated Insulin-Like Growth Factor-1R? Ubiquitination in the Pathogenesis of Alzheimer?s disease

2020 ◽  
Vol 82 ◽  
Author(s):  
HUAN GAO ◽  
XINGJUN WU ◽  
LIHUA CHEN ◽  
LIWEN ZHANG ◽  
YINGFANG ZHANG ◽  
...  
Keyword(s):  
Growth Factor ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Insulin Like Growth Factor ◽  
Neural Precursor Cell ◽  
Protein 4.1

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.

scholarly journals NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor

2005 ◽  
Vol 386 (3) ◽  
pp. 461-470 ◽  
Author(s):  
Go KURATOMI ◽  
Akiyoshi KOMURO ◽  
Kouichiro GOTO ◽  
Masahiko SHINOZAKI ◽  
Keiji MIYAZAWA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ubiquitin Ligases ◽  
Transforming Growth Factor Β ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Type I ◽  
Dependent Manner ◽  
E3 Ubiquitin Ligases ◽  
Neural Precursor Cell

Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs.

Establishment of an epidermal growth factor-dependent, multipotent neural precursor cell line

1998 ◽  
Vol 34 (7) ◽  
pp. 585-592 ◽  
Author(s):  
Yumiko Nakagaito ◽  
Motonobu Satoh ◽  
Haruhiko Kuno ◽  
Toshi Iwama ◽  
Masao Takeuchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Precursor Cell Line ◽  
Epidermal Growth

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.

Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation

2018 ◽  
Vol 17 (2) ◽  
pp. 98-105 ◽  
Author(s):  
Hui Yang ◽  
Yinxiang Yang ◽  
Suqing Qu ◽  
Zhaoyan Wang ◽  
Wei Lu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Mental Retardation ◽  
Growth Factors ◽  
Growth Factor ◽  
Therapeutic Effect ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Short Term ◽  
Before And After

Objective: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT. Methods: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulinlike growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT. Results: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without shortterm therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05). Conclusion: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.

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.

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