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Regulation of p53 by TAF1

Award Number: R01CA075180
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT: The long-term objective of this project is to understand molecular mechanisms involved in regulation of the p53 tumor suppressor. Serving as a checkpoint function to monitor DNA damage, p53 plays a critical role in the regulation of cell proliferation, apoptosis and metabolism. As a DNA-sequence- specific transcription factor, p53 activates transcription of a number of target genes, including the cyclin-dependent kinase inhibitor p21. The transcription activity of p53 is regulated through multiple posttranslational modifications. We previously reported that p53 is phosphorylated at Thr55 by TAF1 (the largest subunit of transcription factor TFIID), leading to p53 inactivation. In the present funding cycle, we made two fundamental discoveries directly related to this renewal: 1) TAF1 phosphorylates p53 on the p21 promoter and this phosphorylation leads to dissociation of p53 from the p21 promoter and turning-off of p53 transcription; and 2) cellular ATP level acts as a molecular switch for TAF1-mediated p53 phosphorylation on the p21 promoter. Our working hypothesis is that TAF1 functions as a cellular ATP sensor, allowing p53-dependent transcription to be regulated in response to cellular metabolism alteration. For this competitive renewal, we seek funding to advance our understanding of this ATP-dependent p53 regulation by TAF1 and address its contribution to cancer. In particular, we propose to uncover how TAF1 kinase activity contributes p53 promoter dissociation in Aim 1. We will answer essential question about how TAF1 senses ATP in Aim 2. Finally, we will explore physiological significance of the regulation in diabetes and cancer in Aim 3. Together, these aims will provide our first detailed understanding of regulation of p53 by TAF1 and its role in cancer.


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: 2024 ( Subtotal = -$1 )
2024	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	20	11/2/2023	NON-COMPETING CONTINUATION	-$1
2024	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	001	20	4/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = -$1

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	20	1/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $369,313 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	20	1/14/2020	NON-COMPETING CONTINUATION	$369,313
														Subtotal = $369,313

Issue Date FY: 2019 ( Subtotal = $358,233 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	19	2/1/2019	NON-COMPETING CONTINUATION	$358,233
														Subtotal = $358,233

Issue Date FY: 2018 ( Subtotal = $368,818 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	18	1/30/2018	NON-COMPETING CONTINUATION	$331,935
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	001	18	5/23/2018	NON-COMPETING CONTINUATION	$36,883
														Subtotal = $368,818

Issue Date FY: 2017 ( Subtotal = $368,125 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	17	1/26/2017	NON-COMPETING CONTINUATION	$331,312
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	001	17	6/7/2017	NON-COMPETING CONTINUATION	$36,813
														Subtotal = $368,125

Issue Date FY: 2016 ( Subtotal = $367,135 )
2016	2016	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	16	2/5/2016	COMPETING CONTINUATION	$367,135
														Subtotal = $367,135

Issue Date FY: 2012 ( Subtotal = $301,913 )
2012	2012	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	15	4/9/2012	NON-COMPETING CONTINUATION	$301,913
														Subtotal = $301,913

Issue Date FY: 2011 ( Subtotal = $301,913 )
2011	2011	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	001	14	5/13/2011	NON-COMPETING CONTINUATION	$21,788
2011	2011	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	14	4/8/2011	NON-COMPETING CONTINUATION	$280,125
														Subtotal = $301,913

Issue Date FY: 2010 ( Subtotal = $311,250 )
2010	2010	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	13	4/6/2010	NON-COMPETING CONTINUATION	$311,250
														Subtotal = $311,250

Issue Date FY: 2009 ( Subtotal = $311,250 )
2009	2009	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	12	3/26/2009	NON-COMPETING CONTINUATION	$311,250
														Subtotal = $311,250

Issue Date FY: 2008 ( Subtotal = $311,250 )
2008	2008	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Cause and Prevention Research	000	11	4/7/2008	COMPETING CONTINUATION	$311,250
														Subtotal = $311,250

Issue Date FY: 2007 ( Subtotal = $49,881 )
2007	2007	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	001	10	7/2/2007	SUPPLEMENT FOR EXPANSION	$49,881
														Subtotal = $49,881

Issue Date FY: 2006 ( Subtotal = $251,496 )
2006	2006	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	000	10	6/26/2006	NON-COMPETING CONTINUATION	$251,496
														Subtotal = $251,496

Issue Date FY: 2005 ( Subtotal = $257,762 )
2005	2005	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	000	9	6/15/2005	NON-COMPETING CONTINUATION	$257,762
														Subtotal = $257,762

Issue Date FY: 2004 ( Subtotal = $257,933 )
2004	2004	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	000	8	7/1/2004	NON-COMPETING CONTINUATION	$257,933
														Subtotal = $257,933

Issue Date FY: 2003 ( Subtotal = $258,606 )
2003	2003	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	000	7	6/27/2003	NON-COMPETING CONTINUATION	$258,606
														Subtotal = $258,606

Issue Date FY: 2002 ( Subtotal = $259,082 )
2002	2002	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Cancer Biology Research	000	6	7/1/2002	COMPETING CONTINUATION	$259,082
														Subtotal = $259,082

Grand Total All Awards = $4,703,959

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Regulation of p53 by TAF1

Award Number: R01CA075180

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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