Version 1
: Received: 4 December 2023 / Approved: 5 December 2023 / Online: 5 December 2023 (14:33:53 CET)
Version 2
: Received: 6 December 2023 / Approved: 6 December 2023 / Online: 7 December 2023 (07:42:01 CET)
Version 3
: Received: 27 December 2023 / Approved: 27 December 2023 / Online: 28 December 2023 (07:13:10 CET)
Ueda, R.; Hashimoto, R.; Fujii, Y.; Menezes, J.C.J.M.D.S.; Takahashi, H.; Takeda, H.; Sawasaki, T.; Motokawa, T.; Tokunaga, K.; Fujita, H. Membrane-Associated Ubiquitin Ligase RING Finger Protein 152 Orchestrates Melanogenesis via Tyrosinase Ubiquitination. Membranes2024, 14, 43.
Ueda, R.; Hashimoto, R.; Fujii, Y.; Menezes, J.C.J.M.D.S.; Takahashi, H.; Takeda, H.; Sawasaki, T.; Motokawa, T.; Tokunaga, K.; Fujita, H. Membrane-Associated Ubiquitin Ligase RING Finger Protein 152 Orchestrates Melanogenesis via Tyrosinase Ubiquitination. Membranes 2024, 14, 43.
Ueda, R.; Hashimoto, R.; Fujii, Y.; Menezes, J.C.J.M.D.S.; Takahashi, H.; Takeda, H.; Sawasaki, T.; Motokawa, T.; Tokunaga, K.; Fujita, H. Membrane-Associated Ubiquitin Ligase RING Finger Protein 152 Orchestrates Melanogenesis via Tyrosinase Ubiquitination. Membranes2024, 14, 43.
Ueda, R.; Hashimoto, R.; Fujii, Y.; Menezes, J.C.J.M.D.S.; Takahashi, H.; Takeda, H.; Sawasaki, T.; Motokawa, T.; Tokunaga, K.; Fujita, H. Membrane-Associated Ubiquitin Ligase RING Finger Protein 152 Orchestrates Melanogenesis via Tyrosinase Ubiquitination. Membranes 2024, 14, 43.
Abstract
Lysosomal degradation of tyrosinase, a pivotal enzyme in melanin synthesis, negatively impacts melanogenesis in melanocytes. Nevertheless, the precise molecular mechanisms by which lysosomes target tyrosinase have remained elusive. Here, we identify RING finger protein 152 (RNF152) as a membrane-associated ubiquitin ligase specifically targeting tyrosinase for the first time, utilizing AlphaScreen technology. We observed that modulating RNF152 levels in B16 melanoma cells, either via overexpression or siRNA knockdown, resulted in decreased or increased tyrosinase levels, respectively. Notably, RNF152 and tyrosinase colocalized at the trans-Golgi network (TGN). However, upon treatment with lysosomal inhibitors, both proteins appeared in the lysosomes, indicating that tyrosinase undergoes RNF152-mediated lysosomal degradation. Through ubiquitination assays, we found the indispensable roles of both the RING and transmembrane (TM) domains of RNF152 in facilitating tyrosinase ubiquitination. In summary, our findings underscore RNF152 as a tyrosinase-specific ubiquitin ligase essential for regulating melanogenesis in melanocytes.
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
7 December 2023
Commenter:
Kenzo Tokunaga
Commenter's Conflict of Interests:
Author
Comment:
We have updated all figures to high-resolution versions. Figure numbers have been removed from the Experimental Procedures section due to the requirement that "Figures should be cited in order." The missing caption for the table has been included. Supplementary material has been referenced in the main text. In the Acknowledgments, "Seiya Ozono" has been amended to "Dr. S. Ozono."
Commenter: Kenzo Tokunaga
Commenter's Conflict of Interests: Author
Figure numbers have been removed from the Experimental Procedures section due to the requirement that "Figures should be cited in order."
The missing caption for the table has been included.
Supplementary material has been referenced in the main text.
In the Acknowledgments, "Seiya Ozono" has been amended to "Dr. S. Ozono."