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ROLE OF WISP39 AND UBIQUITINATION IN P21 FUNCTION

Award Number: R01CA101810
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/09/2004
PERIOD OF PERFORMANCE END DATE: 02/28/2010

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ROLE OF WISP39 AND UBIQUITINATION IN P21 FUNCTION - DESCRIPTION (provided by applicant): p21WAF1/CIP1 protein is a critical p53 transcriptional target, which is required for cell cycle arrest after ionizing radiation. The development of histiocytic sarcomas, hemangiomas/hemangiosarcomas and B cell lymphomas in p21 -/- mice suggests the importance of p21 in cancer. Loss of p21 also increases Adenomatous Polyposis Coil initiated gastrointestinal tumors, increases chemical induced skin carcinoma and cooperates with loss of other tumor suppressors like Rb and p18. p21 has also been shown to play an important role in autoimmunity and stem cell repopulation. It is therefore critical that we understand the regulatory pathways which control p21 protein levels. Although numerous studies have investigated the importance of transcriptional regulation in p21 function, the role of post translational regulation remains less clear. The regulation of p21 proteins levels by post translational mechanisms is the focus of this grant. In preliminary results we describe the identification of a novel protein WISp39 (p39) which stabilizes p21 protein levels. WISp39 acts like an adaptor protein which recruits Hsp90 (via its C-terminal TPR domain) in order to stabilize p21. We propose to investigate in detail the role of Hsp90 binding TPR proteins in regulating p21 stability and function. We will analyze the molecular and functional characteristics of p39 mediated p21 stability using both tissue culture models and whole animal models. By generating p39 -/- mice we will evaluate the functional consequences of p39 on p21 stability in checkpoint control, and tumor generation and development in a whole animal model. Finally we will study the effect of non-ubiquitinated p21 on cell cycle and the cellular response to DNA damage.


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: 2010 ( Subtotal = $5,814 )
2010	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	6	12/21/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$5,814
														Subtotal = $5,814

Issue Date FY: 2009 ( Subtotal = $0 )
2009	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	001	6	7/31/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$45,374
2009	2008	BURNHAM INSTITUTE FOR MEDICAL RESEARCH	10901 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	002	6	8/7/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2009	2008	SIDNEY KIMMEL CANCER CENTER	10905 Road To The Cure	San Diego	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	5	7/31/2009	NON-COMPETING CONTINUATION	-$45,374
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $325,911 )
2008	2008	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	5	2/7/2008	NON-COMPETING CONTINUATION	$325,911
														Subtotal = $325,911

Issue Date FY: 2007 ( Subtotal = $325,911 )
2007	2007	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	4	2/26/2007	NON-COMPETING CONTINUATION	$325,911
														Subtotal = $325,911

Issue Date FY: 2006 ( Subtotal = $335,646 )
2006	2006	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	3	3/27/2006	NON-COMPETING CONTINUATION	$335,646
														Subtotal = $335,646

Issue Date FY: 2005 ( Subtotal = $343,724 )
2005	2005	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	2	3/15/2005	NON-COMPETING CONTINUATION	$343,724
														Subtotal = $343,724

Issue Date FY: 2004 ( Subtotal = $343,724 )
2004	2004	SIDNEY KIMMEL CANCER CENTER	10835 ALTMAN ROW	SAN DIEGO	CA	92121	SAN DIEGO	USA	Cancer Biology Research	000	1	4/9/2004	NEW	$343,724
														Subtotal = $343,724

Grand Total All Awards = $1,680,730

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ROLE OF WISP39 AND UBIQUITINATION IN P21 FUNCTION

Award Number: R01CA101810

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/09/2004

PERIOD OF PERFORMANCE END DATE: 02/28/2010

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