Institute seminar May 7th Sebastian Patzke

Abstract:

The multi-exon CSPP1 gene is encoding for centrosome- and microtubule-associated proteins involved in ciliogenesis and cell division.

We originally identified CSPP1 as a proto-oncogene in diffuse-large-B-cell-lymphoma, and recurrent CSPP1 amplification is observed in several human malignancies, incl. breast cancer. Recently, loss-of-function mutations in CSPP1 were shown as a major cause of Joubert Syndrome, a severe cilia-related developmental disease ("ciliopathy") primarily characterized by manifestations in the central nervous system and most frequently co-occurring with retinal dystrophy, renal cysts, hepatic fibrosis and polydactyly. In short, the deleterious effects of CSPP1 amplification and loss-of-function imply critical functions of CSPP1 proteins in tissue development and homeostasis.

We have studied the molecular functions of CSPP1 proteins by proteomic and (live cell) microscopy approaches in relevant epithelial cell lines in 2-D and 3D culture. This work has identified how CSPP1 proteins are recruited to the centrosome to promote ciliogenesis and aid cell division, and discovered their involvement in cell-cell organization and cyst formation. Further, by studying CSPP1 gene and protein expression in normal mammary tissue, human breast cancer cell lines and primary breast cancer biopsies from two patient cohorts, we (unexpectedly) identified a novel, nuclear localized CSPP1 isoform with a distinct differential expression pattern in the human mammary gland. Importantly, this nuclear CSPP1 isoform identified biologically and clinically distinct subgroups of basal-like breast carcinoma.

I will present a short introduction to our activities and focus on our studies on the centrosome recruitment of CSPP1 proteins and their expression in human breast cancer.

Links:

Sebastian Patzke's publications

Department of Radiation Biology

Insitute seminars, spring season 2014