Transcription factor that regulates copper acquisition and homeostasis, and which plays a central role in fungal pathogenesis during neurologic infection (PubMed:21489137, PubMed:23511945, PubMed:29608794). The transcriptional regulation exerted by CUF1 is intrinsically complex since it acts as a dual sensor of copper levels, responsible for expression of a set of copper-specific copper transporters, CTR1 and CTR4, at low copper concentrations, and 2 metallothioneins, CMT1 and CMT2, at high copper concentrations (PubMed:17290306, PubMed:21489137, PubMed:21819456, PubMed:29608794). Positively regulates the expression of the copper acquisition factor BIM1 under copper-limiting conditions (PubMed:31932719). Also positively regulates the expression of super oxide dismutase SOD2 isoform 2 during oxidative stress and copper-limiting conditions (PubMed:33567338). Negatively regulates the expression of super oxide dismutase SOD1 during copper-limiting conditions (PubMed:33567338). Regulates also ATM1, an ABC transporter with functions in the iron-sulfur clusters (ISC) export machinery, during copper stress (PubMed:29089435). Another target of CUF1 is the gene encoding the laccase LAC1 (PubMed:19459959). Binds promoters of target genes at Cu-responsive elements (CuREs) that contain a variable A/T rich 5' region followed by the core consensus sequence 5'-G(G/C)CTC(A/G)-3' (PubMed:29608794, PubMed:31932719, PubMed:33567338). Negatively regulates capsule biosynthesis, probably via modulating iron acquisition through the high-affinity iron uptake pathway (PubMed:20112673). Upon copper depletion, localizes exclusively to the nucleus as an activator for CTR4 transcription, while it is located to the cell periphery in the presence of exogenous copper. The CRM-I motif (C-X-C-X3-C-X-C-X2-C-X2-H) and CRM-II motif (C-C-X3-C-X-C-X4-C-X-C-X3-C-C-X-C-C-X2-C-X-C) correspond to cystein-rich copper-binding domains. Leads to a clear defect in the ability to grow in both copper excess or copper deficiency conditions (PubMed:29608794). Impairs the activation of laccase LAC1 transcription by copper (PubMed:17290306, PubMed:19459959). Reduces also the expression of the genes coding for the copper transporters CTR1 and CTR4, and the metallothioneins CMT1 and CMT2 (PubMed:21819456). Impairs the induction of the copper acquisition factor BIM1 under copper-limiting conditions (PubMed:31932719). Impairs induction of super oxide dismutase SOD2 under copper-limiting conditions (PubMed:33567338). Impairs repression of super oxide dismutase SOD1 under copper-limiting conditions (PubMed:33567338). Leads to increased cell size and number of mitochondria within the cells, and a higher production of capsules (PubMed:20112673, PubMed:23511945). In copper-limited growth, exhibits copper deficiency, growth defect on glycerol and sensitivity to hydrogen peroxide and methionine (PubMed:17290306, PubMed:21489137). Shows severe hypersensitivity to exogenous copper, while a high level of copper accumulates when copper is in excess (PubMed:21489137). Results in attenuated virulence in an in vivo mouse model of cryptococcosis (PubMed:17290306). In mouse models, exhibits reduced dissemination to the brain, but no change in lung growth (PubMed:17290306). Either you, or me - Issue 228 of September 2020