Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1

Earlier studies of psoriatic and normal primary keratinocytes treated with phorbol 12-myristate-1-acetate identified two low-molecular-weight proteins , termed phorbolin-1 (20 kDa; pi 6.6) and phorbolin-2 (17.6 kDa; pi 6.5), A s a first step towards elucidating the role of these proteins in psoriasis, we report here the molecular cloning and chromosomal mapping of phorbolin- 1 and a related cDNA that codes for a protein exhibiting a similar amino ac id sequence. The phorbolins were mapped to position 22q13 immediately centr omeric to the c-sis proto-oncogene. Transient expression of the phorbolin-1 cDNA in COS cells and by in vitro transcription/translation, yielded polyp eptides that comigrated with phorbolins-1 and -2. Comparative sequence anal ysis revealed 22% overall identity and a similarity of 44% of the phorbolin s to apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme; however, recombinant-expressed phorbolin-1 exhibited no cy tidine deaminase activity, using either a monomeric nucleoside or apolipopr otein B cRNA as substrate, and failed to bind an AU-rich RNA template. Wher eas the precise function of the phorbolins remains to be elucidated, the cu rrent data suggest that it is unlikely to include a role in the post-transc riptional modification of RNA in a manner analogous to that described for a pobec-1.