The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle.

Abstract

Human CAS cDNA contains a 971-aa open reading frame that is homologous to the essential yeast gene CSE1. CSE1 is involved in chromosome segregation and is necessary for B-type cyclin degradation in mitosis. Using antibodies to CAS, it was shown that CAS levels are high in proliferating and low in nonproliferating cells. Here we describe the distribution of CAS in cells and tissues analyzed with antibodies against CAS. CAS is an approximately 100-kDa protein present in the cytoplasm of proliferating cells at levels between 2 x 10(5) and 1 x 10(6) molecules per cell. The intracellular distribution of CAS resembles that of tubulin. In interphase cells, anti-CAS antibody shows microtubule-like patterns and in mitotic cells it labels the mitotic spindle. CAS is removed from microtubules by mild detergent treatment (cytoskeleton preparations) and in vincristine- or taxol-treated cells. CAS is diffusely distributed in the cytoplasm with only traces present in tubulin paracrystals or bundles. Thus, CAS appears to be associated with but not to be an integral part of microtubules. Immunohistochemical staining of frozen tissues shows elevated amounts of CAS in proliferating cells such as testicular spermatogonia and cells in the basal layer cells of the colon. CAS was also concentrated in the respiratory epithelium of the trachea and in axons and Purkinje cells in the cerebellum. These cells contain many microtubules. The cellular location of CAS is consistent with an important role in cell division as well as in ciliary movement and vesicular transport.

20q gain associates with immortalization: 20q13.2 amplification correlates with genome instability in human papillomavirus 16 E7 transformed human uroepithelial cells

“…CAS, which maps to 20q13.2, is the human homolog of the yeast chromosome segregation gene, CSE1 (Xiao et al, 1993). The CSE1 gene product is a microtubule protein involved in chromosome spindle formation; CSE1 mutations lead to a chromosome segregation deficiency phenotype in yeast (Xiao et al, 1993;Scherf et al, 1996). Based on its homology to CSE1, it is reasonable to hypothesize that CAS might play a role in chromosome segregation in human cells.…”

CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs

“…CAS is highly expressed in various cancers (20,21). CAS is an apoptosis susceptibility protein and is also a microtubule-associated protein (22), thus CAS may play an important role in regulating the cytotoxicities of chemotherapeutic drugs (particularly paclitaxel) against cancer cells. We report here that CAS differentially regulates apoptosis of cancer cells induced by paclitaxel and other chemotherapeutic drugs.…”

Ceramide regulation of nuclear protein import

“…CAS concentrations change depending on cell type as well as cellular metabolic state. For example, proliferating cells display higher levels of constitutive CAS than nonproliferating cells (48). Here, CAS was localized to the nucleus of untreated VSMCs.…”