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Superchanneling, Regulation of Caspases, and Site-Specific Control of RNA

Award Number: R01GM031530
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1992
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Superchanneling, Regulation of Caspases, and Site-Specific Control of RNA - Project Summary/Abstract Regulated proteolysis by the ubiquitin-proteasome system (ubiquitin system) plays essential roles in a multitude of biological processes and has major ramifications for human health and disease, including illnesses that range from cancer and neurodegeneration to cardiovascular syndromes and defects of immunity. Our studies of the ubiquitin-proteasome system and ubiquitin-dependent N-degron pathways (previously called “N-end rule pathways”) over more than three decades were made possible, to a large extent, by the present grant (GM031530), currently in its 41st year of support. N-degron pathways recognize proteins containing N-terminal (Nt) degradation signals called N-degrons, polyubiquitylate these proteins and thereby cause their degradation by the proteasome or autophagy. Recognition components of N-degron pathways, called N-recognins, are E3 ubiquitin ligases that can target N-degrons. One eukaryotic N-degron pathway, called the Arg/N-degron pathway, targets, in particular, specific unmodified Nt-residues of protein substrates. This GM031530 renewal application stems from our unpublished studies over the last ~2 years, and focuses on new, previously unexplored aspects of the Arg/N-degron pathway. Specific proposed studies address a coupling between a C-degron and stability of a protein’s mRNA, the new phenomenon of superchanneling in targeting specific degrons, and a functional (as well as mechanistic) link between human caspases and the Arg/N-degron pathway. Our studies of this universally present proteolytic system will contribute to advances in fundamental biology and may also lead to therapies for specific human diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $484,500 )
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	002	43	5/23/2025	NON-COMPETING CONTINUATION	$484,500
2025	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	42	2/18/2025	COMPETING CONTINUATION	$1,187
2025	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	41	2/18/2025	NON-COMPETING CONTINUATION	-$1,187
														Subtotal = $484,500

Issue Date FY: 2024 ( Subtotal = $484,500 )
2024	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	42	8/29/2024	COMPETING CONTINUATION	$484,500
														Subtotal = $484,500

Issue Date FY: 2023 ( Subtotal = $566,100 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	41	11/3/2022	NON-COMPETING CONTINUATION	$509,491
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	41	2/13/2023	NON-COMPETING CONTINUATION	$56,609
														Subtotal = $566,100

Issue Date FY: 2022 ( Subtotal = $566,100 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	40	5/17/2022	NON-COMPETING CONTINUATION	$56,609
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	40	11/12/2021	NON-COMPETING CONTINUATION	$509,491
														Subtotal = $566,100

Issue Date FY: 2021 ( Subtotal = $566,100 )
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	39	11/23/2020	NON-COMPETING CONTINUATION	$509,491
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	39	3/12/2021	NON-COMPETING CONTINUATION	$56,609
														Subtotal = $566,100

Issue Date FY: 2020 ( Subtotal = $597,287 )
2020	2020	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	38	12/12/2019	COMPETING CONTINUATION	$1,187
2020	2020	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	38	12/10/2019	COMPETING CONTINUATION	$596,100
														Subtotal = $597,287

Issue Date FY: 2019 ( Subtotal = -$1,187 )
2019	2018	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	37	7/12/2019	NON-COMPETING CONTINUATION	-$1,187
														Subtotal = -$1,187

Issue Date FY: 2018 ( Subtotal = $589,090 )
2018	2018	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	37	5/16/2018	NON-COMPETING CONTINUATION	$589,090
														Subtotal = $589,090

Issue Date FY: 2017 ( Subtotal = $595,738 )
2017	2017	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	36	5/26/2017	NON-COMPETING CONTINUATION	$595,738
														Subtotal = $595,738

Issue Date FY: 2016 ( Subtotal = $579,593 )
2016	2016	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	35	5/5/2016	NON-COMPETING CONTINUATION	$579,593
														Subtotal = $579,593

Issue Date FY: 2015 ( Subtotal = $600,011 )
2015	2015	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	34	5/8/2015	COMPETING CONTINUATION	$600,011
														Subtotal = $600,011

Issue Date FY: 2014 ( Subtotal = $587,621 )
2014	2014	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	33	5/19/2014	NON-COMPETING CONTINUATION	$587,621
														Subtotal = $587,621

Issue Date FY: 2013 ( Subtotal = $572,813 )
2013	2013	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	32	5/28/2013	NON-COMPETING CONTINUATION	$572,813
														Subtotal = $572,813

Issue Date FY: 2012 ( Subtotal = $605,644 )
2012	2012	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	31	5/17/2012	NON-COMPETING CONTINUATION	$605,644
														Subtotal = $605,644

Issue Date FY: 2011 ( Subtotal = $616,966 )
2011	2011	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	001	30	8/17/2011	COMPETING CONTINUATION	$616,966
2011	2010	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	29	8/16/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $616,966

Issue Date FY: 2010 ( Subtotal = $626,284 )
2010	2010	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	29	4/26/2010	NON-COMPETING CONTINUATION	$626,284
														Subtotal = $626,284

Issue Date FY: 2009 ( Subtotal = $609,703 )
2009	2009	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	28	4/30/2009	NON-COMPETING CONTINUATION	$609,703
														Subtotal = $609,703

Issue Date FY: 2008 ( Subtotal = $592,178 )
2008	2008	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	27	4/11/2008	NON-COMPETING CONTINUATION	$592,178
														Subtotal = $592,178

Issue Date FY: 2007 ( Subtotal = $604,841 )
2007	2007	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	26	4/17/2007	COMPETING CONTINUATION	$604,841
														Subtotal = $604,841

Issue Date FY: 2006 ( Subtotal = $583,302 )
2006	2006	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	25	4/12/2006	NON-COMPETING CONTINUATION	$583,302
														Subtotal = $583,302

Issue Date FY: 2005 ( Subtotal = $589,698 )
2005	2005	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Biomedical Research and Research Training	000	24	4/11/2005	NON-COMPETING CONTINUATION	$589,698
														Subtotal = $589,698

Issue Date FY: 2004 ( Subtotal = $558,053 ) (Continued on the next page)
Grand Total All Awards = $14,881,542

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Superchanneling, Regulation of Caspases, and Site-Specific Control of RNA

Award Number: R01GM031530

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/1992

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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