The of retinoblastoma susceptibility gene product (pRb) is a potent tumor supressor that is frequently mutated in numerous malignancies including leukemias. pRb and related proteins, p107 and p130 binds to and inactivates different members of the E2F family of transcription factors. In addition to E2F pRb can interact with other factors that modulate transcriptional activity of the pRb-E2F complexes such as: HBP1 (HMG-box- containing transcriptional repressor), hBRGl and hBRM (mammalian homologues of SNF2/SWI2 yeast transcription activator), and histone deacetylase (the enzyme involved in chromatin structure rearrangement) have all been reported to interact with pRb and to modulate its transcriptional activity. Binding of each of these modulators to pRb occur in an LXCXE motif-dependent manner. The LXCXE motif was originally found in certain viral oncoproteins (SV40 T antigen, HPV-16 E7, adenoviral E1A) that also are known to bind to pRb. Preliminary results from our laboratory raised a possibility that pRb may also interact with the HMG1/2 class of proteins. The HMG proteins are nuclear, non-histone structural elements of chromatin that contain an LXCXE motif. We propose to investigate whether the HMG class of proteins contributes to the pRb-dependent regulation of transcription. To address this question we will study specific association of HMG2 and pRB in vitro and in vivo model systems. To investigate the functional significance of HMG2/pRb interaction we will examine effect of HMG on pRb ability to repress transcription in model assays.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA084752-03
Application #
6522543
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (01))
Program Officer
Lohrey, Nancy
Project Start
2002-09-01
Project End
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$50,116
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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Chestukhin, Anton; DeCaprio, James A (2003) Western blot screening for monoclonal antibodies against human separase. J Immunol Methods 274:105-13
Chestukhin, Anton; Litovchick, Larisa; Rudich, Katherine et al. (2002) Nucleocytoplasmic shuttling of p130/RBL2: novel regulatory mechanism. Mol Cell Biol 22:453-68