SciP : a novel inhibitor of CtrA transcriptional activity in Caulobacter crescentus

Cells must sense changes in their environment and respond appropriately in order to survive. A common survival strategy is for cells to translate an environmental signal into the activity of a transcription factor they effects a change in gene expression. In this way, cells can express a gene just-in-time for its biological function. In addition, cells can coordinate the activity of many transcription factors to construct genetic regulatory networks that integrate many inputs to control complex cellular behaviors. In this thesis, I use the model system Caulobacter crescentus to examine the regulation of CtrA, the essential transcription factor at the core of the Caulobacter cell cycle regulatory network. CtrA regulates the activity of approximately 100 cell cycle genes many of which are critical for cell cycle progression. CtrA activity is regulated at the level of abundance, post-transcriptional modification, and here I show that CtrA is also regulated by a novel protein-protein interaction. I identify SciP, a GI specific inhibitor of CtrA transcriptional activity and show that SciP forms a complex with CtrA at CtrA dependent promoters. The SciP/CtrA interaction likely prevents CtrA from recruiting RNA polymerase thereby blocking the activation of transcription. In addition, I show that SciP is restricted to G1 by regulated proteolysis. I identify the Lon as the SciP protease and show that Lon is required for SciP proteolysis in vivo and that E. coli Lon degrades SciP in vitro. Finally I engineer a stable allele of sciP and show SciP proteolysis is critical for proper cell cycle progression.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2011

Author dc:creator

• Gora, Kasia G. (Kasia Gabriela)

Advisor dc:contributor.advisor

• Michael T. Laub.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/68426

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/68426