Protein levels in the cell represent the sum of synthesis and degradation. The protein's (genetically encoded) amino acid sequence specifies not only the protein's structure, but also its lifetime through hidden degradation signals encoded in the sequence. Degradation rates balance gene expression rates and thus represent the second half of the equation that determines the active concentration of proteins. In the same way that aberrant gene expression is linked to cancer, so too is aberrant protein processing or degradation. The identity of a protein given by its amino is also dynamic and a combination of sequence elements encoding a degradation initiation signal and a degradation stop signal control the formation of protein fragments with activities distinct from those of the full length protein. This project will decode the sequence signals that shape the proteome and will determine the mechanical and chemical principles underlying these mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143869-05
Application #
8549143
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$179,871
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Hill, Steven M; Heiser, Laura M; Cokelaer, Thomas et al. (2016) Inferring causal molecular networks: empirical assessment through a community-based effort. Nat Methods 13:310-8
Serebryannyy, Leonid A; Parilla, Megan; Annibale, Paolo et al. (2016) Persistent nuclear actin filaments inhibit transcription by RNA polymerase II. J Cell Sci 129:3412-25
Serebryannyy, Leonid A; Cruz, Christina M; de Lanerolle, Primal (2016) A Role for Nuclear Actin in HDAC 1 and 2 Regulation. Sci Rep 6:28460
Zhao, Baobing; Mei, Yang; Schipma, Matthew J et al. (2016) Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening. Dev Cell 36:498-510
Voong, Lilien N; Xi, Liqun; Sebeson, Amy C et al. (2016) Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through Chemical Mapping. Cell 167:1555-1570.e15
Khalkhali-Ellis, Zhila; Kirschmann, Dawn A; Seftor, Elisabeth A et al. (2015) Divergence(s) in nodal signaling between aggressive melanoma and embryonic stem cells. Int J Cancer 136:E242-51
Hornick, Jessica E; Duncan, Francesca E; Sun, Mingxuan et al. (2015) Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg. J Assist Reprod Genet 32:765-9
Kreamer, Naomi N; Phillips, Rob; Newman, Dianne K et al. (2015) Predicting the impact of promoter variability on regulatory outputs. Sci Rep 5:18238
Wells, Daniel K; Chuang, Yishan; Knapp, Louis M et al. (2015) Spatial and functional heterogeneities shape collective behavior of tumor-immune networks. PLoS Comput Biol 11:e1004181
Imakaev, Maxim V; Fudenberg, Geoffrey; Mirny, Leonid A (2015) Modeling chromosomes: Beyond pretty pictures. FEBS Lett 589:3031-6

Showing the most recent 10 out of 156 publications