Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells

Cancer Letters
A HiraiT Moriuchi

Abstract

AIE-75 has been known as a 75-kDa autoantigen detected in the serum of autoimmune enteropathy (AIE) and as a colon cancer-related antigen, and now designated as a gene causative of Usher syndrome type 1C hereditary syndromic hearing loss. It binds to a novel putative tumor suppressor MCC2 that is homologous to MCC (mutated in colon cancer) through a PSD-95/Dlg/ZO-1 (PDZ) domain. To clarify the functional role in colon cancer cells, we transfected AIE-75 gene into SW480 colon cancer cells which do not express AIE-75. Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage, resulting in emergence of hyperploid giant-nucleated or multi-nucleated cells. Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75. Since PP2AC is known to regulate G2/M checkpoint, we suggest that AIE-75 interacts with PP2AC and prevent cells to transit mitotic phase.

References

Nov 1, 1994·The Journal of Cell Biology·P R Andreassen, R L Margolis
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A S AlbertsJ R Feramisco
Jun 1, 1996·Archives of Surgery·D M TakanishiF Michelassi
Jun 4, 1998·International Journal of Cancer. Journal International Du Cancer·M J ScanlanL J Old
Apr 21, 1999·Biochimica Et Biophysica Acta·M J ScanlanL J Old
Sep 29, 1999·Gastroenterology·I KobayashiK Kobayashi
Apr 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·X WuY E Whang
Oct 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jan SiemensUlrich Müller
Mar 7, 2014·Genetics, Selection, Evolution : GSE·Nicholas J BoddickerJack C M Dekkers

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.