New function of Krit 1 and as a new interactor of XAF1 in human colon cancers

Abstract

Background: Suggested that XIAP-associated factor 1 (XAF1) as a potential tumor suppressor as it has recently been shown to negatively regulate the caspase-inhibiting activity of XIAP(X-linked IAP). The Krev interaction trapped-1(Krit1) has been demonstrated mutated in Cerebral Cavernous Malformation families. And the gene located at 7q21-q22, which the region is frequently deleted or amplifi ed in multiple forms of cancer. Objective: Identifi ed the interaction of XAF1 and Krit1,and investigate the novel function of Krit1 in human cancers. Methods: (1) A yeast two-hybrid screen was used to identify the activity of XAF1. (2) Microscopy and coimmunoprecipitation was used to detect the location of Krit1 and confi rmed the interaction of Krit1 and XAF1. (3) RT-PCR was used to investigated the expression of Kirt1 in human colon cancer cells and transient transfection and MTT were used to study Krit1 functions. Results: The Krit1 interacted with XAF1 and colocalized with membrane structures. Krit1 expressed in 7 of 8 human colon cancer cell lines. Overexpression of Krit1 increased 25% of cell death compared with untreated SW1116 cells. Multinucleus cells were induced after 48h combination treatment of Krit1 and XAF1. Conclusions: Krit1 is a novel interactor of XAF1. Krit1 may help determine cancer cell shape and function in response to cell death by guiding cytoskeletal structure and cell cycle.