PMC:4195273 / 83804-85661
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4195273","sourcedb":"PMC","sourceid":"4195273","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4195273","text":"In human, alterations in CART have been associated with reduced metabolic rate, hyperphagia, obesity and elevated incidence of type II diabetes (Banke et al., 2013) (Table 3). For example, a Leu34Phe missense mutation in human proCART was discovered in obese members of an Italian family across three generations to affect post-translational processing, which coincided with CART peptide deficiency in the sera and reduced resting energy expenditure, ultimately leading to hyperphagia and severe early-onset obesity (del Giudice et al., 2001; Dominguez et al., 2004a; Yanik et al., 2006). In brief, the mutation was identified to neighbor a cluster of basic amino acids, hence presupposed to influence the specific processing of the proCART (1–89) in generating the biologically active CART I (42–89) and CART II (49–89) peptides (Kuhar and Yoho, 1999; Thim et al., 1999; del Giudice et al., 2001; Dominguez et al., 2004a). To simulate cellular effects of the mutation, subsequent investigations transfected human CART cDNA constructs representing either the wild-type or the mutant into corticotropic AtT-20 cells, a mouse pituitary-derived cell line often used for studying peptide processing and, more importantly, is known to express and process CART peptides (Dominguez et al., 2004a). Notably, in addition to reduced CART peptide levels in cells transfected with the mutated cDNA compared with controls, expression of the mutated proCART was also described to be mis-sorted, poorly processed and secreted, thus disarranging the cellular distribution of CART as a whole (Dominguez et al., 2004a). Other than discoveries that addressed the potentially crucial role of protein biosynthesis in the development of obesity, the majority of the studies directed at the association between CART and obesity focused on polymorphisms in CART within populations.","tracks":[{"project":"TEST0","denotations":[{"id":"25352770-159-167-357882","span":{"begin":159,"end":163},"obj":"[\"23318496\"]"},{"id":"25352770-224-232-357883","span":{"begin":537,"end":541},"obj":"[\"11522684\"]"},{"id":"25352770-228-236-357885","span":{"begin":582,"end":586},"obj":"[\"16210370\"]"},{"id":"25352770-235-243-357886","span":{"begin":847,"end":851},"obj":"[\"10420164\"]"},{"id":"25352770-227-235-357887","span":{"begin":866,"end":870},"obj":"[\"10077578\"]"},{"id":"25352770-234-242-357888","span":{"begin":892,"end":896},"obj":"[\"11522684\"]"}],"attributes":[{"subj":"25352770-159-167-357882","pred":"source","obj":"TEST0"},{"subj":"25352770-224-232-357883","pred":"source","obj":"TEST0"},{"subj":"25352770-228-236-357885","pred":"source","obj":"TEST0"},{"subj":"25352770-235-243-357886","pred":"source","obj":"TEST0"},{"subj":"25352770-227-235-357887","pred":"source","obj":"TEST0"},{"subj":"25352770-234-242-357888","pred":"source","obj":"TEST0"}]},{"project":"0_colil","denotations":[{"id":"25352770-23318496-357882","span":{"begin":159,"end":163},"obj":"23318496"},{"id":"25352770-11522684-357883","span":{"begin":537,"end":541},"obj":"11522684"},{"id":"25352770-16210370-357885","span":{"begin":582,"end":586},"obj":"16210370"},{"id":"25352770-10420164-357886","span":{"begin":847,"end":851},"obj":"10420164"},{"id":"25352770-10077578-357887","span":{"begin":866,"end":870},"obj":"10077578"},{"id":"25352770-11522684-357888","span":{"begin":892,"end":896},"obj":"11522684"}],"attributes":[{"subj":"25352770-23318496-357882","pred":"source","obj":"0_colil"},{"subj":"25352770-11522684-357883","pred":"source","obj":"0_colil"},{"subj":"25352770-16210370-357885","pred":"source","obj":"0_colil"},{"subj":"25352770-10420164-357886","pred":"source","obj":"0_colil"},{"subj":"25352770-10077578-357887","pred":"source","obj":"0_colil"},{"subj":"25352770-11522684-357888","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"25352770-23318496-38284871","span":{"begin":159,"end":163},"obj":"23318496"},{"id":"25352770-11522684-38284872","span":{"begin":537,"end":541},"obj":"11522684"},{"id":"25352770-16210370-38284874","span":{"begin":582,"end":586},"obj":"16210370"},{"id":"25352770-10420164-38284875","span":{"begin":847,"end":851},"obj":"10420164"},{"id":"25352770-10077578-38284876","span":{"begin":866,"end":870},"obj":"10077578"},{"id":"25352770-11522684-38284877","span":{"begin":892,"end":896},"obj":"11522684"}],"attributes":[{"subj":"25352770-23318496-38284871","pred":"source","obj":"2_test"},{"subj":"25352770-11522684-38284872","pred":"source","obj":"2_test"},{"subj":"25352770-16210370-38284874","pred":"source","obj":"2_test"},{"subj":"25352770-10420164-38284875","pred":"source","obj":"2_test"},{"subj":"25352770-10077578-38284876","pred":"source","obj":"2_test"},{"subj":"25352770-11522684-38284877","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#93ecd5","default":true},{"id":"0_colil","color":"#ecbb93"},{"id":"2_test","color":"#a093ec"}]}]}}