Interaction of HRP-2 isoforms with HDGF: chromatin binding of a specific heteromer.
Hepatoma-derived growth-factor-related protein 2 (HRP-2) belongs to a family with five additional members: hepatoma-derived growth factor (HDGF); lens epithelium-derived growth factor; and the HDGF-related proteins -1, -3 and -4. Very little is known regarding the function of HRP-2 in particular. This study shows for the first time heteromer formation of different members of the HRP family; HDGF and HRP-2. In addition, we discovered a previously unknown splice variant of HRP-2 mRNA encoding for a protein with a 53-amino acid deletion in its hath region. This HRP-2 isoform c interacts preferentially with a processed form of HDGF probably because of the loss of an α helix of HRP-2. Furthermore, in contrast to other isoforms of HRP-2, isoform c binds to chromatin similar to its most closely related family member lens epithelium-derived growth factor with potential consequences regarding its function in HIV integration. Interestingly, only the new HRP-2 isoform c and a processed form of HDGF are displaced from condensed mitotic metaphase chromatin. In conclusion, these observations provide a new perspective for understanding the biological functions of HDGF and related proteins.
Department of Biochemistry, Centre for Biomolecular Interactions Bremen (CBIB), University of Bremen, Germany.
Ketan
K
Thakar
Ina
I
Votteler
Dipti
D
Kelkar
Teja
T
Shidore
Shivangi
S
Gupta
Sørge
S
Kelm
Frank
F
Dietz
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000502:physiology
D002843:Chromatin; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C051610:hepatoma-derived growth factor; C119380:lens epithelium-derived growth factor