DDB_G0272777 - dictyBase/community-annotations GitHub Wiki

DDB G0272777 appears to be the Dicty-specific, AAA-ATPase related cdc48 (cdcD) in Dicty and other organisms. When "blasted out" DDB_G0272777 hits cdc48 and cdc48-related proteins in many organisms, but when these are blasted back to Dicty, cdcD rather than DDB_G0272777 is always the first hit.

Cdc48 is an ubiquitin-associated chaperone which is involved in the degradation of a variety of cellular proteins, particularly proteins trapped in macromolecular structures, which must be mobilized for degradation. Cdc48 is ascribed a major role in the ERAD (ER-associated degradation) pathway in which proteins that fail to fold properly are retransported to the cytosol and degraded by the ubiquitin-proteasome pathway. The gene was originally named, however for a cell-cycle associated defect in yeast: at the restrictive temperature, ts mutants arrest in late M phase with sister chromatids separated but with a single nucleus extending into both mother and daughter cells. This phenotype has been convincingly associated with a loss of the ability of ER-derived vesicles to fuse in vitro, see Latterich et al, Cell 82 (1995). The cdc48 mitotic phenotype may result from an inability for nuclear membrane fusion required in nuclear fission. More recent work has identified a variety of other roles for cdc48 in mitosis, see Meyer and Popp, Biochemical Society Transactions 36, (2008).

DDB G0272777 is fourfold overexpressed (p 10e-10) in a Dicty strain lacking the retinoblastoma-like gene rblA (Doquang et al, in preparation). Most genes involved in DNA replication, centrosome duplication and mitosis are overexpressed in this strain, typically by factors from 5x to 20x. This supports the idea that DDB G0272777 is involved in Dicty cell cycle progression. CdcD, by constrast, shows virtually no overpression in the rblA disruptant (induction factor in mutant ca 1,1). An interesting possibility is that DDB_G0272777 has diverged from cdcD and specialized for mitotic function, while the nonmitotic functions of cdc48 have been taken over by cdcD.

Harry MacWilliams, December 2009

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