Abstract

The research focuses on the mechanism by which Abelson murine leukemia virus (Ab-MLV) induces lymphomas and transforms lymphoid cells. The role of Abl in triggering growth, suppressing apoptosis and driving the selection of tumor suppressor mutations in Tp53 and Mts1 will be examined.
Four specific aims will addressed. The first examines the selection of Tp53 mutations, including the type of mutations, the kinetics at which they arise and the forces that drive their selection. The second specific aim studies the altered expression of p16 protein in vivo and in vitro, as it relates to Ab-MLV mediated transformation. The third specific aim utilizes a recently discovered Ab-MLV mutant which does not stimulate growth but does suppress apoptosis. This mutant leads to changes in the Bcl-x protein and altered cleavage of PARP, a substrate for the ICE proteases. The pathways by which v-Abl induces these signals and suppresses apoptosis will be examined. The last specific aim studies the mechanism by which v-Abl disrupts control of G1 transit.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033771-19
Application #
6375658
Study Section
Virology Study Section (VR)
Program Officer
Cole, John S
Project Start
1983-06-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
19
Fiscal Year
2001
Total Cost
$316,969
Indirect Cost

  Institution

Name
Tufts University
Department
Pathology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Zimmerman, Rebekah Stackpole; Rosenberg, Naomi (2008) Changes in p19Arf localization accompany apoptotic crisis during pre-B-cell transformation by Abelson murine leukemia virus. J Virol 82:8383-91
Yi, Chae-ryun; Rosenberg, Naomi (2008) Mutations affecting the MA portion of the v-Abl protein reveal a conserved role of Gag in Abelson murine leukemia virus (MLV) and Moloney MLV. J Virol 82:5307-15
Finstad, Samantha L; Rosenberg, Naomi; Levy, Laura S (2007) Diminished potential for B-lymphoid differentiation after murine leukemia virus infection in vivo and in EML hematopoietic progenitor cells. J Virol 81:7274-9
Yi, Chae-Ryun; Rosenberg, Naomi (2007) Gag influences transformation by Abelson murine leukemia virus and suppresses nuclear localization of the v-Abl protein. J Virol 81:9461-8
Desgranges, Zana P; Ahn, Jinwoo; Lazebnik, Maria B et al. (2005) Inhibition of TFII-I-dependent cell cycle regulation by p53. Mol Cell Biol 25:10940-52
Gong, Li; Unnikrishnan, Indira; Raghavan, Anuradha et al. (2004) Active Akt and functional p53 modulate apoptosis in Abelson virus-transformed pre-B cells. J Virol 78:1636-44
Sachs, Zohar; Sharpless, Norman E; DePinho, Ronald A et al. (2004) p16(Ink4a) interferes with Abelson virus transformation by enhancing apoptosis. J Virol 78:3304-11
Unnikrishnan, Indira; Rosenberg, Naomi (2003) Absence of p53 complements defects in Abelson murine leukemia virus signaling. J Virol 77:6208-15
Mostecki, J; Halgren, A; Radfar, A et al. (2000) Loss of heterozygosity at the Ink4a/Arf locus facilitates Abelson virus transformation of pre-B cells. J Virol 74:9479-87
Jenab-Wolcott, J; Rodriguez-Correa, D; Reitmair, A H et al. (2000) The absence of Msh2 alters abelson virus pre-B-cell transformation by influencing p53 mutation. Mol Cell Biol 20:8373-81

Showing the most recent 10 out of 23 publications