Oscar R Colamonici
Email Address: ocolamon@uic.eduCollege: Medicine Department: Pharmacology
Office: 410 CMW M/C 868 Phone: 4134113
Participating in the Chancellor’s Undergraduate Research Awards program: No
Research Interest:
RESEARCH PLANS The main research focus of our lab has centered on the role of the mammalian orthologs of the Drosophila dREAM complex in cell cycle regulation. The two projects currently underway can be summarized as follows. Regulation of G1 by Mip/LIN-9 Understanding the mechanisms that govern cell cycle progression is important for the development of novel therapeutic agents against cancer. The G1 phase is a critical crossroad where positive and negative regulatory signals converge to control cell cycle progression. The family of pocket proteins is responsible for restricting cell cycle progression via the formation of repressor complexes with E2F and DP family members, which result in the inhibition of E2F target genes. We cloned a novel gene, named Mip130/LIN-9, which regulates cell cycle progression. Our studies demonstrate that deletion of the first 84 amino acids of Mip130/LIN-9 (Mip130/LIN-9∆84) corrects the CDK4 null phenotype. Therefore, Mip130/LIN-9, like the pocket proteins pRB, p107 and p130, is negatively regulated by CDK4. Interestingly, the correction of the CDK4 null phenotype is accompanied by a restoration of the expression of genes such as E2F1, E2F3, and cyclin E suggesting that Mip130/LIN-9 participates in the regulation of E2F target genes required for the G1/S transition. This is further supported by the finding that Mip130/LIN-9 interacts with two members of the pocket family, p107 and p130. The objectives of this project are: 1) To characterize the mechanism that leads to the correction of the CDK4 null phenotype by the mutation ∆84 of Mip130/LIN-9. 2) To test the hypothesis that Mip130/LIN-9 is part of the transcriptional repressor complex formed by p107,130/E2F4,5/DPs and that its interaction with other members of the complex is required for the regulation of the expression of E2F target genes responsible for cell cycle progression. Regulation of S phase and mitosis by Mip/LIN-9. In Drosophila, the homolog of Mip130/LIN-9, Mip130, is part of a large complex termed dREAM (drosophila RB, E2F and Myb) that includes pocket proteins, repressor forms of E2F, B-Myb and B-Myb-interacting proteins termed Mip(s) such as Mip40/LIN-37 and Mip120/LIN-54. In Drosophila, this complex inhibits transcription of specific genes and duplication of specific genomic regions. Our data suggest that the mammalian equivalent of Mip130, Mip40 and Mip120 (Mip130/LIN-9, Mip40/LIN-37 and Mip120/LIN-54) form a stable complex termed MCC/LINC (Mip Core Complex or LIN, Complex), which also includes Sin3b. Unlike the Drosophila counterpart, the MCC/LINC specifically interacts with p107/p130, E2F4 and HDAC1 in G0 and early G1, and with B-Myb in late G1 and S phase. Moreover, while the MMC/LINC association with E2F4 and p107 or p130 has a repressor effect, the interaction with B-Myb is responsible for the transcriptional activation of critical S-phase and mitotic genes such as cyclin A, cyclin B and CDK1. We are currently characterizing the role of mammalian Mip40/LIN-37 and Mip120/LIN-54 in cell cycle regulation and development. Publications Deletion of the p107/p130-binding domain of Mip130/LIN-9 bypasses the requirement for CDK4 activity for the dissociation of Mip130/LIN-9 from p107/p130-E2F4 complex. Sandoval R, Pilkinton M, Colamonici OR. Exp Cell Res. 2009 Oct 15;315(17):2914-20. Mip/LIN-9 can inhibit cell proliferation independent of the pocket proteins. Pilkinton M, Sandoval R, Barrett K, Tian X, Colamonici OR. Blood Cells Mol Dis. 2007 Nov-Dec;39(3):272-7. Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex. Pilkinton M, Sandoval R, Colamonici OR. Oncogene. 2007 Nov 29;26(54):7535-43. Mip/LIN-9 regulates the expression of B-Myb and the induction of cyclin A, cyclin B, and CDK1. Pilkinton M, Sandoval R, Song J, Ness SA, Colamonici OR. J Biol Chem. 2007 Jan 5;282(1):168-75. Minimum time commitment in hours per week: 10-12 Qualifications of a Student:
GPA of 3.5 or higher. Lab experience is preferred but not required. Brief Summary of what is expected from the student:
Applicants should work part time during the academic year (min 10hr/week) and dedicate at least 30hr/week during the summer and other holidays.
NOTE: This researcher is currently not accepting applications for the Undergraduate Research Experience program.
