{"id":1561,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/mechanisms-of-menin-action\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"mechanisms-of-menin-action","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/mechanisms-of-menin-action\/","title":{"rendered":"MECHANISMS OF MENIN ACTION"},"content":{"rendered":"
Sunita K. Agarwal, Atsushi Ozawa, Terri S. Rice, Van Wang, Shadia Zaman, Caitlin M. Quigley, Carmen M. Mateo, A. Lee Burns, William F. Simonds, H.-C Jennifer Shen, Steven K. Libutti, Sukhbir Kaur, Settara C Chandrasekharappa, Francis S. Collins, Stephen J. Marx<\/div>\n
Metabolic Diseases Branch NIDDK, Genome Technology Branch NHGRI, Surgery Branch NO, All from the National Institutes of Health, Bethesda, MD USA.<\/div>\n
Background:<\/strong> Discovery of the MEN1 gene in 1997 predicted an encoded molecule (men in) with no homologies or identifiable domains. MEN1-related tumors had a loss of MEN 1 function, evidenced by loss of heterozygosity at 11 q13. MEN1 sequencing confirmed inactivation of both alleles of MEN 1 in many MEN1 tumors and in many common tumors. Loss of function provides no insight into menin's cellular compartment or menin's molecular mechanism. ln fact, loss of menin function in many tissues is not sufficient to cause any other change. <\/p>\n

Objectives & Methods:<\/strong> Present current status of work to understand menin mechanisms. Use published and unpublished data.

Menin partners in protein or in chromatin:<\/strong> Menin actions have been studied maninly with menin partnering methods in normal or tumorigenic cells. We identified several menin partners: junO, NF-Kb, RPA-2, and non-muscle myosin heavy chain IIA. Combining the results from all laboratories, some 25 protein partners of menin have been identified. They do not establish a clear pattern except that most are in the nucleus. We have also found that menin binds directly or indirectly to hundreds of chromatin sites, including many outside of gene promoters. It remains to be proved that all or perhaps even any of these protein or chromatin partners is the central mediator of all tumorigenesis by menin. <\/p>\n

Menin tumorigenicity via partnering with Jun D or MLL:<\/strong> Greatest attention has been directed at junO and MLL as possibly pathologic menin partners. We have found that menin inactivation can switch junO from a growth suppressor to a growth promoter. Others have found that menin in a COMPASS complex can activate transcription of p18 and p27 growth inhibitors. When this is lost, growth promotion can result. <\/p>\n

Menin actions downstream:<\/strong> Molecules and pathways downstream of menin's initial partners have been analyzed. Several studies have pointed to one or more HOX genes. Other Genes for MEN1: MEN1-like states in rodents (termed MENX) and man (termed MEN4 by Online Mendelian Inheritance of Man (OM 1M)) have implicated mutation of the p27Kip1 (CDKN1 B) cyclin-dependent kinase inhibitor as an alternate and rare cause of MEN1. All of this suggests that MEN 1 and p27 have common steps in their tumor paths. <\/p>\n

Conclusion and Speculations:<\/strong> Major aspects of the menin pathways remain unconfirmed. Understanding the pathways could lead to novel drugs for the rare tumors ofMEN1 and for many common tumors. <\/div>\n","protected":false},"excerpt":{"rendered":"

Sunita K. Agarwal, Atsushi Ozawa, Terri S. Rice, Van Wang, Shadia Zaman, Caitlin M. Quigley, Carmen M. Mateo, A. Lee Burns, William F. Simonds, H.-C Jennifer Shen, Steven K. Libutti, Sukhbir Kaur, Settara C Chandrasekharappa, Francis S. Collins, Stephen J. Marx Metabolic Diseases Branch NIDDK, Genome Technology Branch NHGRI, Surgery Branch NO, All from the Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[52,2,11],"tags":[],"class_list":["post-1561","post","type-post","status-publish","format-standard","hentry","category-volume-9-issue-2","category-journal-articles","category-volume-9"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1561","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1561"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1561\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1561"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1561"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1561"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}