An Analysis of Political Contributions from Otolaryngologists in the United States.

OBJECTIVE: Doctors can influence the development of sound healthcare policy through financial contributions to political campaigns and candidates. Our objective was to characterize the political contributions of otolaryngologists in the United States, both individually and through the ENT Political Action Committee (ENTPAC) between the years 2003 and 2020. STUDY DESIGN: Retrospective observational study. SETTING: Publicly available information on the internet: fec.gov. METHODS: The Federal Election Commission's website, fec.gov, was used to identify the political contributions of individual otolaryngologists and the ENTPAC between 2003 and 2020. Each contribution is associated with a political group or candidate, designated as a Republican, Democratic, or Independent entity. RESULTS: A total of 1407 distinct political contributions were made by individuals identifying as otolaryngologists between 2003 and 2020, totaling $432,201. Overall, Republicans received more individual donations than Democrats (711 vs 540), while Democrats received more money ($231,139 vs $183,427). Donations peaked during election years, with the total amount overall increasing each election year ($9664 in 2004 vs $75,102 in 2020). The predominant political party receiving donations between 2003 and 2020 in each US state matched each state's predominant party of the governors and senators 48.6% of the time. The ENTPAC donated $3,027,383 between 2003 and 2020 to a variety of political candidates and entities. CONCLUSION: Otolaryngologists are making increased political contributions over time and interest in political advocacy may be at an all-time high. Increased time and attention should be devoted to educating otolaryngologists to best politically advocate for interests which are of the most importance to themselves and the profession.

TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.

The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell proliferation and tumor burden after TMEM127 loss can be reversed by selective RET inhibitors in vitro and in vivo. Our results define TMEM127 as a component of the ubiquitin system and identify aberrant RET stabilization as a likely mechanism through which TMEM127 loss-of-function mutations cause pheochromocytoma.