A new member of a hepatoma-derived growth factor gene family can translocate to the nucleus.
Hepatoma-derived growth factor (HDGF) and HDGF-related proteins (HRP) belong to a gene family with a well-conserved amino acid sequence at the N-terminus (the hath region). A new member of the HDGF family in humans and mice was identified and cloned; we call it HRP-3. The deduced amino acid sequence from HRP-3 cDNA contained 203 amino acids without a signal peptide for secretion. HRP-3 has its 97-amino-acid sequence at the N-terminus, which is highly conserved with the hath region of the HDGF family proteins. It also has a putative bipartite nuclear localizing signal (NLS) sequence in a similar location in its self-specific region of HDGF and HRP-1. Northern blot analysis shows that HRP-3 is expressed predominantly in the testis and brain, to an intermediate extent in the heart, and to a slight extent in the ovaries, kidneys, spleen, and liver in humans. Transfection of green fluorescent protein (GFP)-tagged HRP-3 cDNA showed that HRP-3 translocated to the nucleus of 293 cells. GFP-HRP-3 transfectants significantly increased their DNA synthesis more than cells transfected with vector only. The HRP-3 gene was mapped to chromosome 15, region q25 by FISH analysis. These findings suggest that a new member of the HDGF gene family, HRP-3, may function mainly in the nucleus of the brain, testis, and heart, probably for cell proliferation.
Ikegame
K
K
Department of Molecular Medicine, Osaka University Medical School, Yamada-oka 2-2, Suita, Osaka, 565-0871, Japan.
Yamamoto
M
M
Kishima
Y
Y
Enomoto
H
H
Yoshida
K
K
Suemura
M
M
Kishimoto
T
T
Nakamura
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006133:Growth Substances; C498539:HDGFL3 protein, human; C402392:Hdgfl3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C051610:hepatoma-derived growth factor; D004247:DNA