PMID- 11738826 OWN - NLM STAT- MEDLINE DCOM- 20020228 LR - 20190707 IS - 0378-1119 (Print) IS - 0378-1119 (Linking) VI - 280 IP - 1-2 DP - 2001 Dec 12 TI - Identification of a novel family of putative methyltransferases that interact with human and Drosophila presenilins. PG - 135-44 AB - Mutations in the presenilin genes have been shown to cause the majority of cases of early-onset familial Alzheimer's disease (AD). In addition to their role in AD, presenilins are also known to function during development by interacting with the Notch pathway. To determine if presenilins have additional functions during development and AD we have used a yeast two-hybrid approach to search for proteins that can bind to presenilins. Here, we show the identification and characterization of a novel putative methyltransferase (Metl) that interacts with the loop region of Drosophila presenilin as well as human presenilin-1 and presenilin-2, suggesting that this interaction is evolutionarily conserved and functionally important. Metl appears to be a member of a conserved family of methyltransferases that share homology with, but are distinct from, the UbiE family of methyltransferases involved in ubiquinone and menaquinone biosynthesis. In Drosophila, the metl gene gives rise to two major isoforms by alternative splicing that are broadly expressed throughout development and found in the central nervous system in an overlapping pattern with Drosophila presenilin. Finally, we show that two independent dominant adult phenotypes produced by overexpression of presenilin can be enhanced by overexpression of metl in the same tissue. Taken together, these results suggest that presenilin and Metl functionally and genetically interact during development. FAU - Zhang, S X AU - Zhang SX AD - Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Ontario, Toronto, Canada. FAU - Guo, Y AU - Guo Y FAU - Boulianne, G L AU - Boulianne GL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Isoenzymes) RN - 0 (Membrane Proteins) RN - 0 (PSEN1 protein, human) RN - 0 (PSEN2 protein, human) RN - 0 (Presenilin-1) RN - 0 (Presenilin-2) RN - 0 (RNA, Messenger) RN - EC 2.1.1.- (Methyltransferases) SB - IM MH - Alternative Splicing MH - Amino Acid Sequence MH - Animals MH - Drosophila/embryology/genetics/growth & development MH - Female MH - Gene Expression Regulation, Developmental MH - Gene Expression Regulation, Enzymologic MH - Genes/genetics MH - Humans MH - Isoenzymes/genetics/metabolism MH - Male MH - Membrane Proteins/genetics/*metabolism MH - Methyltransferases/*genetics/metabolism MH - Molecular Sequence Data MH - Presenilin-1 MH - Presenilin-2 MH - Protein Binding MH - RNA, Messenger/genetics/metabolism MH - Saccharomyces cerevisiae/genetics MH - Sequence Homology, Amino Acid MH - Two-Hybrid System Techniques EDAT- 2001/12/12 10:00 MHDA- 2002/03/01 10:01 CRDT- 2001/12/12 10:00 PHST- 2001/12/12 10:00 [pubmed] PHST- 2002/03/01 10:01 [medline] PHST- 2001/12/12 10:00 [entrez] AID - S0378-1119(01)00770-3 [pii] AID - 10.1016/s0378-1119(01)00770-3 [doi] PST - ppublish SO - Gene. 2001 Dec 12;280(1-2):135-44. doi: 10.1016/s0378-1119(01)00770-3.