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CaaX Protein Processing and Human Disease

Description: The proteins of the nuclear lamina have generated enormous interest because of recent studies showing that genetic defects in nuclear lamins cause multiple human diseases. The main objective of this renewal application is to continue to explore the physiologic and medical relevance of the posttranslational processing of the nuclear lamins, particularly as it relates to devastating neuronal migration defects and the pathogenesis and treatment of progeroid syndromes (precocious aging syndromes). Our studies will be focused on the physiologic importance of the B-type lamins in the developing brain and other tissues and the physiologic importance of the posttranslational processing of prelamin A.
Funding type: research
Funder scheme: R01
Start date: 2003-08-15
End date: 2015-06-30
Investigator: STEPHEN G. YOUNG
Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES
Funded outputs count: 43
Funder award ID: R01AG035626
OpenAlex ID: G4522303692
Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina
2024 · Paul H. Kim, Joonyoung R. Kim, et al. · Proceedings of the National Academy of Sciences · 21
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Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies
2020 · Natalie Y. Chen, Paul H. Kim, et al. · Nucleus · 18
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GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism
2019 · Stephen G. Young, Loren G. Fong, et al. · Cell Metabolism · 142
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Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome
2018 · Paul H. Kim, Jennings Luu, et al. · Science Translational Medicine · 79
Lamin B1 is required for mature neuron-specific gene expression during olfactory sensory neuron differentiation
2017 · Crystal M. Gigante, Michele Dibattista, et al. · Nature Communications · 32
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Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24
2016 · Shahid Mehmood, Julien Marcoux, et al. · Nature Chemistry · 65
Modulation of LMNA splicing as a strategy to treat prelamin A diseases
2016 · John M. Lee, Chika Nobumori, et al. · Journal of Clinical Investigation · 111
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Nuclear Envelope Protein Lem2 is Required for Mouse Development and Regulates MAP and AKT Kinases
2015 · Olga Tapia, Loren G. Fong, et al. · PLoS ONE · 36
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Mice that express farnesylated versions of prelamin A in neurons develop achalasia
2015 · Shao H. Yang, Shiri Procaccia, et al. · Human Molecular Genetics · 12
An Absence of Nuclear Lamins in Keratinocytes Leads to Ichthyosis, Defective Epidermal Barrier Function, and Intrusion of Nuclear Membranes and Endoplasmic Reticulum into the Nuclear Chromatin
2014 · Hea-Jin Jung, Angelica Tatar, et al. · Molecular and Cellular Biology · 24
Do lamin B1 and lamin B2 have redundant functions?
2014 · John M Lee, Hea-Jin Jung, et al. · Nucleus · 16
Nuclear Lamins and Neurobiology
2014 · Stephen G. Young, Hea-Jin Jung, et al. · Molecular and Cellular Biology · 52
Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2
2014 · John M. Lee, Yiping Tu, et al. · Molecular Biology of the Cell · 28
New Lmna knock-in mice provide a molecular mechanism for the ‘segmental aging’ in Hutchinson–Gilford progeria syndrome†
2013 · Hea-Jin Jung, Yiping Tu, et al. · Human Molecular Genetics · 22
Circumventing Embryonic Lethality with Lcmt1 Deficiency: Generation of Hypomorphic Lcmt1 Mice with Reduced Protein Phosphatase 2A Methyltransferase Expression and Defects in Insulin Signaling
2013 · Kennen B. MacKay, Yiping Tu, et al. · PLoS ONE · 14
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Targeting Isoprenylcysteine Methylation Ameliorates Disease in a Mouse Model of Progeria
2013 · Mohamed X. Ibrahim, Volkan I. Sayin, et al. · Science · 124
Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration
2013 · Hea-Jin Jung, Chika Nobumori, et al. · Proceedings of the National Academy of Sciences · 85
Targeting Protein Prenylation in Progeria
2013 · Stephen G. Young, Shao H. Yang, et al. · Science Translational Medicine · 62
Targeting GGTase-I Activates RHOA, Increases Macrophage Reverse Cholesterol Transport, and Reduces Atherosclerosis in Mice
2013 · Omar M. Khan, Murali K. Akula, et al. · Circulation · 53
Nuclear Lamins in the Brain — New Insights into Function and Regulation
2012 · Hea-Jin Jung, John M. Lee, et al. · Molecular Neurobiology · 40
Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation in cells by inhibiting ZMPSTE24
2012 · Sandy Y. Chang, Sarah E. Hudon-Miller, et al. · Journal of Lipid Research · 21
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Understanding the Roles of Nuclear A- and B-type Lamins in Brain Development
2012 · Stephen G. Young, Hea-Jin Jung, et al. · Journal of Biological Chemistry · 59
Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA
2012 · Hea-Jin Jung, Catherine Coffinier, et al. · Proceedings of the National Academy of Sciences · 221
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Are B-type lamins essential in all mammalian cells?
2011 · Shao H. Yang, Hea-Jin Jung, et al. · Nucleus · 47
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Severe hepatocellular disease in mice lacking one or both CaaX prenyltransferases
2011 · Shao H. Yang, Sandy Y. Chang, et al. · Journal of Lipid Research · 16
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