Skip navigation
Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/20155
Title: LRSAM1 E3 ubiquitin ligase promotes proteasomal clearance of E6-AP protein
Authors: Mishra R.
Joshi V.
Upadhyay A.
Amanullah A.
Dubey A.R.
Singh S.
Dubey V.K.
Poluri, Krishna Mohan
Jana N.R.
Mishra A.
Published in: Cellular Signalling
Abstract: Numerous proteins participate and actively contribute to the various cellular mechanisms, where several of them are crucial for regular metabolism, including survival. Thus, to maintain optimal cellular physiology, cells govern protein quality control functions with the assistance of comprehensive actions of molecular chaperones, the ubiquitin-proteasome system, and autophagy. In the ubiquitin-proteasome pathway, few quality control E3 ubiquitin ligases actively participate against misfolded protein aggregation generated via stress conditions. But how these quality control E3s active expression levels returned to basal levels when cells achieved re-establishment of proteostasis is still poorly understood. Our current study demonstrated that LRSAM1 E3 ubiquitin ligase promotes the proteasomal degradation of quality control E3 ubiquitin ligase E6-AP. We have observed the co-localization and recruitment of LRSAM1 with E6-AP protein and noticed that LRSAM1 induces the endogenous turnover of E6-AP. Partial depletion of LRSAM1 elevates the levels of E6-AP and affects overall cell cycle regulatory proteins (p53 and p27) expression, including the rate of cellular proliferation. The current finding also provides an excellent opportunity to better understand the basis of the E6-AP associated pathomechanism of Angelman Syndrome disorder. Additionally, this study touches upon the novel potential molecular strategy to regulate the levels of one quality control E3 ubiquitin ligase with another E3 ubiquitin ligase and restore proteostasis and provide a possible therapeutic approach against abnormal protein aggregation diseases. © 2020 Elsevier Inc.
Citation: Cellular Signalling, 77
URI: https://doi.org/10.1016/j.cellsig.2020.109836
http://repository.iitr.ac.in/handle/123456789/20155
Issue Date: 2021
Publisher: Elsevier Inc.
Keywords: Chaperone
E6-AP
LRSAM1
Misfolded proteins
Neurodegeneration
Proteasome
ISSN: 8986568
Author Scopus IDs: 56767511300
56189143600
57189335137
56188291700
57214335712
8621706700
7005789615
55842079400
7006695923
57214220793
Author Affiliations: Mishra, R., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Joshi, V., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Upadhyay, A., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Amanullah, A., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Dubey, A.R., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Singh, S., Department of Neuroscience and Ageing Biology and Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, UP 226031, India
Dubey, V.K., School of Biochemical Engineering, Indian Institute of Technology BHU, Varanasi, 221005, India
Poluri, K.M., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
Jana, N.R., School of Bioscience Indian Institute of Technology Kharagpur, Kharagpur, 721302, India
Mishra, A., Cellular and Molecular Neurobiology Unit, Indian Institute of Technology JodhpurRajasthan 342037, India
Funding Details: The research grant of EMR/2016/000716 was provided to AM from Science and Engineering Research Board (SERB) , Department of Science & Technology, Government of India. VJ and AU obtained a research fellowship from the University Grants Commission , Council for Scientific and Industrial Research, Government of India. We are also thankful to Mr. Bharat Pareek for his technical assistance and lab management during the manuscript preparation. LRSAM1-Myc expression construct was a kind gift from Dr. Robert Burgess of The Jackson Laboratory, USA. We are grateful to Douglas T Golenbock MD (Medical School, University of Massachusetts, Worcester USA) for pcDNA3-EGFP or pcDNA-EGFP and to Dr. Wafik S, El-Deiry (Fox Chase cancer center, Philadelphia, USA) for pcDNA3-cMyc or pcDNA-Myc plasmid. Jackson Laboratory, JAX; Department of Science and Technology, Ministry of Science and Technology, India, डीएसटी; Council of Scientific and Industrial Research, India, CSIR; University Grants Commission, UGC; Science and Engineering Research Board, SERB
Corresponding Author: Mishra, A.; Cellular and Molecular Neurobiology Unit, India; email: amit@iitj.ac.in
Appears in Collections:Journal Publications [BT]

Files in This Item:
There are no files associated with this item.
Show full item record


Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.