Lethal Giant Larvae Tumor Suppressor Research Articles

The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p

Rab guanosine triphosphatases regulate intracellular membrane traffic by binding specific effector proteins. The yeast Rab Sec4p plays multiple roles in the polarized transport of post-Golgi vesicles to, and their subsequent fusion with, the plasma membrane, suggesting the involvement of several effectors. Yet, only one Sec4p effector has been documented to date: the exocyst protein Sec15p. The exocyst is an octameric protein complex required for tethering secretory vesicles, which is a prerequisite for membrane fusion. In this study, we describe the identification of a second Sec4p effector, Sro7p, which is a member of the lethal giant larvae tumor suppressor family. Sec4-GTP binds to Sro7p in cell extracts as well as to purified Sro7p, and the two proteins can be coimmunoprecipitated. Furthermore, we demonstrate the formation of a ternary complex of Sec4-GTP, Sro7p, and the t-SNARE Sec9p. Genetic data support our conclusion that Sro7p functions downstream of Sec4p and further imply that Sro7p and the exocyst share partially overlapping functions, possibly in SNARE regulation.

Molecular cloning and characterization of bovine bgl-1, a novel family member of WD-40 repeat-containing lethal giant larvae tumor suppressor genes

In this study, we have isolated a bovine homologue bgl-1 of lethal giant larvae (lgl) tumor suppressor oncogene from bovine brain by RT-PCR using primers designed based on the conserved sequences for lgl family members. The sequence analysis showed that the bgl-1 encodes a 1,036 amino acid polypeptide with the molecular weight of approximately 112 kDa containing a domain characteristic of WD-40 proteins. The amino acid sequence of bgl-1 showed a homology of 98.3 and 87.3% identity to that of mouse and human, respectively. Northern blot analysis showed that bgl-1 was highly expressed in brain, ovary and testis, with moderate expression in liver, uterus, lung and kidney. This suggests that the bgl-1 may play essential roles in each of these organs. The complementation analysis revealed that the bovine bgl-1 partially restored the Na+ tolerance in the absence of yeast lgl homologue, suggesting that bgl-1 is a bovine homologue of the lgl family.