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). As 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 acid sequence. The phorbolins were mapped to position 22q13 immediately centromeric to the c-sis proto-oncogene. Transient expression of the phorbolin-1 cDNA in COS cells and by in vitro transcription/translation, yielded polypeptides that comigrated with phorbolins-1 and -2. Comparative sequence analysis revealed 22% overall identity and a similarity of 44% of the phorbolins to apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme; however, recombinant-expressed phorbolin-1 exhibited no cytidine deaminase activity, using either a monomeric nucleoside or apolipoprotein B cRNA as substrate, and failed to bind an AU-rich RNA template. Whereas the precise function of the phorbolins remains to be elucidated, the current data suggest that it is unlikely to include a role in the post-transcriptional modification of RNA in a manner analogous to that described for apobec-1.
Madsen
P
P
Department of Medical Biochemistry, University of Aarhus, Denmark. pm@biokemi.au.dk
Anant
S
S
Rasmussen
H H
HH
Gromov
P
P
Vorum
H
H
Dumanski
J P
JP
Tommerup
N
N
Collins
J E
JE
Wright
C L
CL
Dunham
I
I
MacGinnitie
A J
AJ
Davidson
N O
NO
Celis
J E
JE
D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003564:Cytidine Deaminase / Q000737:chemistry / Q000502:physiology*; D015723:Gene Library; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011565:Psoriasis / Q000503:physiopathology*; D017386:Sequence Homology, Amino Acid; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase