Overexpression of human glycolipid transfer protein transcript (GLTP), but not novel splice variants GLTP_v1 or GLTP_v2, induces apoptosis

Abstract

Glycolipid transfer protein (GLTP) accelerates glycolipid intermembrane transfer and serves as the conformational prototype defining the conserved GLTP superfamily. In humans, the single‐copy GLTP gene at 12q24.11 encodes the five‐exon GLTP transcript. Herein, two previously unknown GLTP splice variants are identified and functionally evaluated. Exon1 was the only exon common to the GLTP, GLTP_v1, and GLTP_v2 transcripts. In GLTP_v1, a new exon has been discovered within sequence previously designated GLTP intron2. The GLTP splice variants are highly tissue specific compared to the more ubiquitous GLTP transcript. Immunolocalization reveals distribution of exogenously‐expressed GLTP_i1 and GLTP_i2 throughout HeLa cells and, unlike GLTP, presence within nuclei. Exogenous GLTP expression induces S phase cell cycle arrest and apoptosis in HeLa cells. The pro‐apoptotic effect of GLTP occurs independently of glycolipid binding/transfer. In contrast, exogenous expression of GLTP_v1 and GLTP_v2 protects cells from apoptosis induced by hydrogen peroxide or etoposide without altering the cell cycle. Neither GLTP splice variant affects the expression or glycolipid transfer activity of GLTP. The data show for the first time that overexpression of GLTP, but not GLTP_v1 or GLTPv2, induces cell apoptosis, underscoring the biological diversity of the GLTP gene [Support: NIH GM45928, CA121493 & Hormel Fnd.]