caa a22 4500 606236945 CHVBK 20210128101250.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s11010-014-2309-7 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2309-7 Cullin 4A and 4B ubiquitin ligases interact with γ-tubulin and induce its polyubiquitination [Elektronische Daten] [Anand Thirunavukarasou, Gokulapriya Govindarajalu, Prachi Singh, Venkateshwarlu Bandi, Kannan Muthu, Sudhakar Baluchamy] Regulated polyubiquitination is a key step for controlling protein degradation and maintaining proper balance between the proliferation of normal and uncontrolled cells. Addition of ubiquitin to the proteins by E3 ubiquitin ligases targets them for degradation by the 26S proteosome machinery. Discrepancies in ubiquitination and/or proteosome degradation might lead to multiple genetic disorders in humans. It is reported that CUL1 and BRCA1 ubiquitin ligases localize on centrosome region and regulate the centrosome duplication cycle for genomic stability. In the current study, we predicted the possible interaction of E3 ubiquitin ligase CUL4A complex with γ-tubulin, a centrosome-specific protein, using bioinformatic protein-protein docking analysis. We also confirmed their interaction by performing co-immunoprecipitation studies using endogenous CUL4A/B and stable cell lines that overexpress Flag-CUL4A or Flag-CUL4B. We additionally noted that the γ-tubulin was polyubiquitinated by CUL4A or 4B immune complex indicating that CUL4A or CUL4B may regulate the stability of γ-tubulin. Furthermore, the inhibition of proteosomal degradation pathway using MG132 or LLNV drugs resulted in accumulation and co-localization of CUL4A with γ-tubulin in the centrosome region. Overall, our observation has identified γ-tubulin as a novel target for E3 ubiquitin ligase CUL4 complex, and might lead to the establishment of a unique mechanism for controlling centrosome stability. Springer Science+Business Media New York, 2014 E3 ubiquitin ligase nationallicence Tubulin nationallicence Centrosome nationallicence Protein-protein interaction nationallicence Ubiquitination nationallicence Protein degradation nationallicence Thirunavukarasou Anand Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut Govindarajalu Gokulapriya Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut Singh Prachi Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut Bandi Venkateshwarlu Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut Muthu Kannan Centre for Bioinformatics, Pondicherry Central University, 605014, Pondicherry, India aut Baluchamy Sudhakar Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 219-228 0300-8177 401:1-2<219 2015 401 11010 https://doi.org/10.1007/s11010-014-2309-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2309-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Thirunavukarasou Anand Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut NATIONALLICENCE 700 1- Govindarajalu Gokulapriya Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut NATIONALLICENCE 700 1- Singh Prachi Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut NATIONALLICENCE 700 1- Bandi Venkateshwarlu Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut NATIONALLICENCE 700 1- Muthu Kannan Centre for Bioinformatics, Pondicherry Central University, 605014, Pondicherry, India aut NATIONALLICENCE 700 1- Baluchamy Sudhakar Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 219-228 0300-8177 401:1-2<219 2015 401 11010