Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.

Current Biology : CB
Hua YanCathie M Pfleger

Abstract

The Ras signaling pathway allows cells to translate external cues into diverse biological responses. Depending on context and the threshold reached, Ras signaling can promote growth, proliferation, differentiation, or cell survival. Failure to maintain precise control of Ras can have adverse physiological consequences. Indeed, excess Ras signaling disrupts developmental patterning and causes developmental disorders [1, 2], and in mature tissues, it can lead to cancer [3-5]. We identify Rabex-5 as a new component of Ras signaling crucial for achieving proper pathway outputs in multiple contexts in vivo. We show that Drosophila Rabex-5 restricts Ras signaling to establish organism size, wing vein pattern, and eye versus antennal fate. Rabex-5 has both Rab5 guanine nucleotide exchange factor (GEF) activity that regulates endocytic trafficking [6] and ubiquitin ligase activity [7, 8]. Surprisingly, overexpression studies demonstrate that Rabex-5 ubiquitin ligase activity, not its Rab5 GEF activity, is required to restrict wing vein specification and to suppress the eye phenotypes of oncogenic Ras expression. Furthermore, genetic interaction experiments indicate that Rabex-5 acts at the step of Ras, and tissue culture studies show t...Continue Reading

References

Oct 18, 2003·Seminars in Cancer Biology·Anja M Duursma, Reuven Agami
Jul 6, 2004·Nature Immunology·See-Ying TamStephen J Galli
Sep 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Carl-Johan ZettervallDan Hultmark
Nov 1, 2005·Nature Cell Biology·Han Lu, David Bilder
Jan 10, 2006·Human Molecular Genetics·Kimihiko OishiBruce D Gelb
Feb 8, 2006·Nature Structural & Molecular Biology·Sangho LeeJames H Hurley
Mar 2, 2006·Molecular Cell·Natalia JuraDafna Bar-Sagi
Mar 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Janet KalesnikoffStephen J Galli
Jul 29, 2006·Annual Review of Genetics·Iswar K Hariharan, David Bilder
Feb 17, 2009·Cancer Letters·Clara Montagut, Jeff Settleman
May 27, 2009·Current Opinion in Genetics & Development·William E Tidyman, Katherine A Rauen
Jul 15, 2009·Advances in Cancer Research·Amy YoungFrank McCormick
Jul 27, 2010·Current Biology : CB·Lizhong XuDafna Bar-Sagi

❮ Previous
Next ❯

Citations

Oct 11, 2012·The Journal of Biological Chemistry·Yoshikatsu AikawaSangho Lee
Jun 25, 2014·ELife·Zhe ZhangJianping Ding
Nov 15, 2011·The International Journal of Biochemistry & Cell Biology·Kerstin KrauseDagmar Fuhrer
Oct 30, 2015·Proceedings of the National Academy of Sciences of the United States of America·Linda FabrisGustavo Baldassarre
Dec 7, 2011·Small GTPases·Michelle de la VegaJames A Johnston
Jun 28, 2012·Small GTPases·Ze-Yi ZhengEric C Chang
Jul 27, 2010·Current Biology : CB·Lizhong XuDafna Bar-Sagi
Aug 10, 2010·Current Biology : CB·John Colicelli
Sep 15, 2012·Developmental Cell·Michael J ClagueSylvie Urbé
Apr 22, 2014·Cell Reports·Taoling ZengHong-Rui Wang
Nov 15, 2014·Cells·Zoi ErpapazoglouRosine Haguenauer-Tsapis
Feb 3, 2012·Physiological Reviews·Sara SigismundPier Paolo Di Fiore
Feb 18, 2016·EMBO Molecular Medicine·Maria Francesca BaiettiAnna A Sablina
May 19, 2011·The Journal of Biological Chemistry·Hiroaki KajihoToshiaki Katada
Jun 20, 2020·PLoS Genetics·Chalita WashingtonCathie M Pfleger
Nov 18, 2018·Science·Johannes W BigenzahnGiulio Superti-Furga
Oct 28, 2019·The Journal of Biological Chemistry·Henrik G Dohlman, Sharon L Campbell
Apr 9, 2016·Small GTPases·Gustavo Baldassarre, Barbara Belletti
Jun 27, 2019·Cancer Research·Luca D'AgostinoNan Gao
Apr 4, 2020·Molecular Cancer Therapeutics·Lihua ShuZhuo G Chen
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Imran KhanJohn P O'Bryan
Apr 5, 2021·Seminars in Cancer Biology·Wei DaiByeong Hyeok Choi
Dec 21, 2020·Neoplasia : an International Journal for Oncology Research·Chun-Jung LinJer-Tsong Hsieh
Nov 15, 2015·Journal of Cell Science·Theresa A Reimels, Cathie M Pfleger
May 13, 2014·Journal of Cell Science·Behzad RowshanravanDavid A Hughes
Jul 27, 2021·Frontiers in Molecular Biosciences·Natsuki OsakaAtsuo T Sasaki
Aug 9, 2021·Current Opinion in Structural Biology·Sharon L Campbell, Mark R Philips
Mar 10, 2011·Science Signaling·Cathie M Pfleger

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.