BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export.

Proceedings of the National Academy of Sciences of the United States of America
Kaochin NgeowColin R Goding

Abstract

The close integration of the MAPK, PI3K, and WNT signaling pathways underpins much of development and is deregulated in cancer. In principle, combinatorial posttranslational modification of key lineage-specific transcription factors would be an effective means to integrate critical signaling events. Understanding how this might be achieved is central to deciphering the impact of microenvironmental cues in development and disease. The microphthalmia-associated transcription factor MITF plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts, and mast cells and acts as a lineage survival oncogene in melanoma. MITF coordinates survival, differentiation, cell-cycle progression, cell migration, metabolism, and lysosome biogenesis. However, how the activity of this key transcription factor is controlled remains poorly understood. Here, we show that GSK3, downstream from both the PI3K and Wnt pathways, and BRAF/MAPK signaling converges to control MITF nuclear export. Phosphorylation of the melanocyte MITF-M isoform in response to BRAF/MAPK signaling primes for phosphorylation by GSK3, a kinase inhibited by both PI3K and Wnt signaling. Dual phosphorylation, but not monophosphorylation, then p...Continue Reading

References

Jul 11, 1998·The Journal of Biological Chemistry·E R PriceD E Fisher
Apr 5, 2000·The Journal of Biological Chemistry·K TakedaS Shibahara
Jan 1, 2004·Chemistry & Biology·Laurent MeijerPaul Greengard
Oct 28, 2004·The Journal of Biological Chemistry·Arlo J MillerDavid E Fisher
Mar 9, 2005·Trends in Cell Biology·Ulrike Kutay, Stephan Güttinger
Jul 21, 2005·Pigment Cell Research·Hideki Murakami, Heinz Arnheiter
Dec 22, 2006·Genes & Development·Suzanne CarreiraColin R Goding
Mar 14, 2009·Nature Genetics·David DankortMarcus Bosenberg
Aug 24, 2010·Pigment Cell & Melanoma Research·Keith S Hoek, Colin R Goding
Dec 9, 2010·Science Signaling·Ariel BensimonYosef Shiloh
Oct 21, 2011·Nature·Corine BertolottoBrigitte Bressac-de Paillerets
May 3, 2012·Genes & Development·Liesbeth C W VredeveldDaniel S Peeper
Feb 13, 2013·The Journal of Cell Biology·Jose A Martina, Rosa Puertollano
Mar 13, 2013·Cancer Cell·Rizwan HaqHans R Widlund
Mar 23, 2013·Science·Shukry J HabibRoel Nusse
Jun 22, 2013·Human Molecular Genetics·Christine GrillEiríkur Steingrímsson
Jul 9, 2013·The Journal of Investigative Dermatology·James A ListerE Elizabeth Patton
Nov 5, 2013·Nature·Cory M JohannessenLevi A Garraway
Nov 10, 2013·The Journal of Clinical Investigation·Victoria Marsh DurbanMartin McMahon
Nov 29, 2013·Current Topics in Medicinal Chemistry·David H DrewryWilliam J Zuercher
Apr 29, 2014·Cancer Discovery·David J KonieczkowskiLevi A Garraway
Sep 3, 2014·British Journal of Cancer·I V FedorenkoK S M Smalley

❮ Previous
Next ❯

Citations

May 28, 2019·Genes & Development·Colin R Goding, Heinz Arnheiter
Oct 3, 2019·Genes & Development·Florian RambowColin R Goding
Jul 15, 2020·International Journal of Molecular Sciences·Anna Gajos-Michniewicz, Malgorzata Czyz
Sep 4, 2020·PloS One·Josué Ballesteros-ÁlvarezEiríkur Steingrímsson
Apr 10, 2020·Frontiers in Cell and Developmental Biology·Meriem BejaouiHiroko Isoda
Aug 28, 2020·Pigment Cell & Melanoma Research·Hong Nhung VuEiríkur Steingrímsson
Jun 13, 2020·Molecular Cell·Pakavarin LouphrasitthipholColin R Goding
May 25, 2021·The Journal of Investigative Dermatology·Yu WangHongguang Lu
May 12, 2021·Molecules and Cells·Seongryong KimYou-Me Kim
Aug 4, 2021·Journal of Proteome Research·Bohui LiMaarten Altelaar
Aug 27, 2021·Molecular Cancer Therapeutics·Paul RossmanDeborah W Knapp

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.