Thesis
Sp1 nontranscriptionally regulates centrosome number
Master of Science (M.S.), Drexel University
29 Mar 2016
DOI:
https://doi.org/10.17918/00008731
Abstract
Specificity protein 1 (Sp1) is a highly conserved transcription factor ubiquitously expressed in mammalian tissues. Sp1 regulates a myriad of processes including cell cycle progression, apoptosis and the DNA damage response. Sp1 is overexpressed in many cancer types and is a poor prognostic indicator. RNAi-induced knockdown of Sp1 results in elevated continuous chromosome missegregation, also known as whole chromosomal instability (CIN). CIN is a major characteristic of cancer and is associated with poor patient prognosis. Therefore, understanding the relationship between Sp1 and CIN could have strong therapeutic impact. One potential mechanism linking Sp1 depletion and CIN is centrosome amplification, a phenomenon shown to contribute to CIN. Previously, we reported that Sp1 localizes to the centrosome and that depletion of Sp1 results in centrosome amplification (Astrinidis, et al 2010). Further, this process appears to be independent of Sp1's function as a transcription factor. A truncated form of Sp1 lacking the N-terminal 182 amino acids, which retains 91% of Sp1's transcriptional activity, fails to localize to the centrosome and fails to rescue the supernumerary centrosome phenotype we see in Sp1 depleted cells. We show here that the 182 amino acid N-terminal portion of Sp1 can localize to the centrosome. Importantly, this mutant is not transcriptionally active, indicating that Sp1 transcriptional activity is not required for its centrosomal localization. Further, RNAi-mediated depletion of full length Sp1 and re-expression of this this N-terminal mutant can rescue the supernumerary centrosome phenotype. Taken together, these data indicate that Sp1 regulates centrosome number in a non-transcriptional manner.
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Details
- Title
- Sp1 nontranscriptionally regulates centrosome number
- Creators
- Samuel Flashner
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vi, 36 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Medicine; Drexel University
- Other Identifier
- 991021888729304721