Monday, January 19, 2026 1/19/2026

Regulation of transcriptional activation by protein disorder

Award Number: R01GM115556
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: 06/01/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

Regulation of transcriptional activation by protein disorder - Regulation of transcriptional activation by protein disorder PIs: Daughdrill/Chen Abstract The p53 tumor suppressor is a sequence-specific DNA binding protein that activates gene transcription to regulate cell survival and proliferation. It is mutated in at least 50% of solid tumors and some of these mutants are oncogenic and activate the transcription of genes that promote cell survival and metastasis. Despite decades of research on p53, there are currently no FDA approved drugs in the clinic that directly target wt or mutant p53. This is, in part, because 50% of p53 is disordered and we have an incomplete understanding of what these regions look like and how they function. We have recently shown that the disordered N-terminal acidic transactivation domain of p53 (NT) dynamically interacts with the DNA binding domain (DBD) with residues that contact DNA. This interaction inhibits DNA binding but increases binding specificity using a combination of nucleic acid mimicry and electrostatic shielding that enhances recognition of promoter binding sites in vivo. We propose to: (1) Determine the specific effects of nucleic acid mimicry and electrostatic shielding on DNA binding specificity, and how tethering controls the intramolecular interaction between NT and DBD. (2) Investigate how p53 NT phosphorylation regulates DNA binding affinity and specificity to create adaptable switching of transcriptional activation. (3) Determine how MdmX interferes with p53 DNA binding when it forms a heterodimer with p53. Successful completion of these experiments will lead to a better understanding of how p53 governs cell fate after DNA damage by regulating the binding specificity to pro-survival versus pro-apoptotic target genes. A deeper understanding of the structural and functional properties of the weak dynamic interactions within p53 and between p53 and MdmX is necessary for the successful development of small molecules to target these interactions for cancer therapy.


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: 2026 ( Subtotal = $0 )
2026	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	8	1/15/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $371,405 )
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	001	8	8/9/2023	SUPPLEMENT FOR EXPANSION	$51,191
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	8	6/29/2023	NON-COMPETING CONTINUATION	$320,214
														Subtotal = $371,405

Issue Date FY: 2022 ( Subtotal = $319,459 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	7	6/28/2022	NON-COMPETING CONTINUATION	$319,459
														Subtotal = $319,459

Issue Date FY: 2021 ( Subtotal = $318,706 )
2021	2021	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	002	6	7/7/2021	NON-COMPETING CONTINUATION	$318,706
2021	2020	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	001	5	6/11/2021	COMPETING CONTINUATION	$95,702
2021	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	4	6/11/2021	NON-COMPETING CONTINUATION	-$95,702
														Subtotal = $318,706

Issue Date FY: 2020 ( Subtotal = $330,442 )
2020	2020	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	001	5	8/25/2020	COMPETING CONTINUATION	$330,442
2020	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	4	8/17/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $330,442

Issue Date FY: 2019 ( Subtotal = $311,085 )
2019	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	4	5/11/2019	NON-COMPETING CONTINUATION	$311,085
														Subtotal = $311,085

Issue Date FY: 2018 ( Subtotal = $311,491 )
2018	2018	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	3	5/3/2018	NON-COMPETING CONTINUATION	$311,491
														Subtotal = $311,491

Issue Date FY: 2017 ( Subtotal = $311,845 )
2017	2017	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	2	6/8/2017	NON-COMPETING CONTINUATION	$311,845
														Subtotal = $311,845

Issue Date FY: 2016 ( Subtotal = $322,052 )
2016	2016	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	1	5/25/2016	NEW	$322,052
														Subtotal = $322,052

Grand Total All Awards = $2,596,485

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of transcriptional activation by protein disorder

Award Number: R01GM115556

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: 06/01/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer