At least two regions of the oncoprotein Tre2 are involved in its lack of GAP activity.
The product of the human Tre2 oncogene is structurally related to the Ypt/Rab GTPase-activating proteins (Ypt/Rab GAPs). Particularly, the oncoprotein shares with the yeast proteins Msb3p and Msb4p, and with the human protein RN-tre the highly conserved TBC domain, forming the catalytically active domain of Ypt/Rab GAPs. Yet, the Tre2 oncogene seems to encode a nonfunctional Rab GAP. As regions flanking the TBC domain may be crucial for catalytic activity, regions located N- and C-terminally with respect to this domain were explored. For this, chimeric proteins created by sequence exchanges between the Tre2 oncoprotein and RN-tre were tested for their ability to replace functionally the Msb3p and Msb4p proteins in double-mutant yeast cells. These complementation experiments revealed, in addition to the TBC domain, a second Tre2 region involved in the oncoprotein's lack of GAP activity: a 93-aa region flanking the TBC domain on the C-terminal side.
Bizimungu
Christelle
C
Animal and Microbial Biology Unit, Gembloux Agricultural University, B-5030 Gembloux, Belgium. bizimungu.c@fsagx.ac.be
Vandenbol
Micheline
M
D001483:Base Sequence; D017931:DNA Primers; D010450:Endopeptidases / Q000737:chemistry / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
D017931:DNA Primers; D020690:GTPase-Activating Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase