Molecular and Structural Traits of Insulin Receptor Substrate 1/LC3 Nuclear Structures and Their Role in Autophagy Control and Tumor Cell Survival.

Molecular and Cellular Biology
Adam LassakKrzysztof Reiss

Abstract

Insulin receptor substrate 1 (IRS-1) is a common cytosolic adaptor molecule involved in signal transduction from insulin and insulin-like growth factor I (IGF-I) receptors. IRS-1 can also be found in the nucleus. We report here a new finding of unique IRS-1 nuclear structures, which we observed initially in glioblastoma biopsy specimens and glioblastoma xenografts. These nuclear structures can be reproduced in vitro by the ectopic expression of IRS-1 cDNA cloned in frame with the nuclear localization signal (NLS-IRS-1). In these structures, IRS-1 localizes at the periphery, while the center harbors a key autophagy protein, LC3. These new nuclear structures are highly dynamic, rapidly exchange IRS-1 molecules with the surrounding nucleoplasm, disassemble during mitosis, and require a growth stimulus for their reassembly and maintenance. In tumor cells engineered to express NLS-IRS-1, the IRS-1/LC3 nuclear structures repress autophagy induced by either amino acid starvation or rapamycin treatment. In this process, IRS-1 nuclear structures sequester LC3 inside the nucleus, possibly preventing its cytosolic translocation and the formation of new autophagosomes. This novel mechanism provides a quick and reversible way of inhibiting ...Continue Reading

References

Feb 1, 1994·Current Opinion in Genetics & Development·M F White
Jul 17, 1998·Experimental Cell Research·K ReissR Baserga
Apr 15, 2000·Nature·R D Phair, T Misteli
Apr 3, 2001·Nature Reviews. Genetics·T Cremer, C Cremer
Jan 16, 2002·Current Biology : CB·Jens S AndersenAngus I Lamond
Mar 6, 2002·The Journal of Biological Chemistry·Adam LassakKrzysztof Reiss
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Angus I Lamond, David L Spector
Jun 1, 2004·Molecular Biology of the Cell·Noriko SaitohDavid L Spector
Nov 10, 2004·The Journal of Biological Chemistry·An WuRenato Baserga
Jan 7, 2005·Nature·Jens S AndersenMatthias Mann
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·Dirk LebrechtUlrich A Walker
Jul 6, 2007·Autophagy·Noboru Mizushima, Tamotsu Yoshimori
Jun 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Jul 17, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mohamed AbdouhGilbert Bernier
Mar 31, 2010·PloS One·Kimberly R DrakeAnne K Kenworthy
Jul 30, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sabrina FacchinoGilbert Bernier
Oct 10, 1995·Applied Optics·V KrishnamurthiT J Holmes
Nov 12, 2010·Cold Spring Harbor Perspectives in Biology·Miroslav Dundr, Tom Misteli
Jun 18, 2011·Trends in Genetics : TIG·Yuntao S MaoDavid L Spector
Dec 19, 2013·Journal of Cell Science·Philipp WildIvan Dikic
Jan 5, 2014·Chinese Journal of Cancer·Andreas F HottingerKrisztian Homicsko
Mar 14, 2014·Frontiers in Endocrinology·Atsufumi OzoeShin-Ichiro Takahashi
Mar 19, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Oct 22, 2014·Molecular and Cellular Biology·Anna WilkKrzysztof Reiss
Nov 8, 2014·Neoplasia : an International Journal for Oncology Research·Luis MarreroOm Prakash
May 24, 2016·Cell·Marina FericClifford P Brangwynne
Aug 4, 2016·Autophagy·Anne-Claire JacominIoannis P Nezis

❮ Previous
Next ❯

Citations

May 16, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Iman AbdollahzadehThomas Gensch

❮ Previous
Next ❯

Related Concepts

Related Feeds

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Related Papers

Advances in Experimental Medicine and Biology
S A RosenzweigB S Miller
Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Xian-Ling GuoLi-Xin Wei
Sheng li ke xue jin zhan [Progress in physiology]
B Y Liu, H X Wang
© 2022 Meta ULC. All rights reserved