Abstract
Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults with high metastasis rates. D-type cyclins (CCNDs) are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer. Recently, the E3 ligase adaptor, autophagy and beclin 1 regulator 1 (AMBRA1), was reported to regulate the stability of CCNDs, including CCND1, but its role in UVM has not been demonstrated. AMBRA1 is lowly expressed in UVM cells, and the ablation of AMBRA1 promotes the proliferation of 92.1 and OMM1 cells, whereas ectopically expressing AMBRA1 attenuates the proliferation of UVM cells. Further studies found that AMBRA1 promotes the ubiquitination and degradation of CCND1, and AMBRA1 regulates the proliferation of UVM cells in a CCND1-dependent manner. Thus, this study suggests that AMBRA1 serves as an important tumor suppressor by limiting UVM cell growth.
Highlights
Uveal melanoma (UVM) is a melanoma of the eyes, which arises from melanocytes in the uvea, 90% of which# These authors contributed to this work.The ocular treatment usually aims to conserve the eyeball, preserving the visual performance
Researchers from three collaborating teams of scientists in the United States and Europe found that AMBRA1 marks CCNDs involved in helping cells divide for destruction when cell division is not needed [13,14,19]
AMBRA1 serves as an important tumor suppressor by limiting tumor growth
Summary
Uveal melanoma (UVM) is a melanoma of the eyes, which arises from melanocytes in the uvea, 90% of which. Targeted therapy is widely used in cancer treatment due to its lesser side effects compared to other strategies. Protein ubiquitination is a dynamic multifaceted posttranslational modification involved in most aspects of eukaryotic biology, including cancer development and progression, cell survival and differentiation, innate and adaptive immunity, and individual development and sexual maturity [7,8,9]. Ubiquitination includes a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types [10], including UVM. D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer [12]. The function of AMBRA1 in UVM was extensively studied
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
