A novel TAT fusion protein with osteoinductive activity.
Osteoblasts are thought to be differentiated from pluripotent mesenchymal stem cells. Several intracellular and extracellular osteoinductive proteins are involved in this process. Such proteins include the bone morphogenetic proteins (BMPs) and the LIM mineralization proteins (LMPs) etc. LMP-1 is a novel LIM domain protein promoting the differentiation of osteoblasts during bone formation. It contains three LIM domains/motifs, one PDZ domain and a unique sequence. Through analysis of the amino acid sequence and the function of the LMPs, it has been found that the PDZ domain (1-93 aa) and a unique region (94-133 aa) appear to be critical for bone formation. The TAT protein of human immunodeficiency virus can be fused with other macromolecules, peptides or proteins and transport them into cells successfully. Once being transduced into cells, the fusion protein can recover its biological activity through being rapidly refolded. We supposed that TAT could be fused with LMP-1 (1-133 aa) and LMP-1 (94-133 aa) and the fusion proteins could be easily transduced through biological membranes and generate biological activity. The clinical application of BMPs has been limited for their relatively high cost and the unstable osteoinductivity. If the hypothesis proved to be practical, we would have a more effective new way to promote bone repair and regeneration.
Zhang
Da-Wei
DW
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, 17 Changle Western Road, Xi'an 710032, China.
Li
Li-Wen
LW
Hu
Yun-Yu
YY
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation; D002459:Cell Fusion; D003598:Cytoskeletal Proteins; D015696:Gene Products, tat; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D060588:LIM Domain Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis; D017434:Protein Structure, Tertiary; D014161:Transduction, Genetic
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D003598:Cytoskeletal Proteins; D015696:Gene Products, tat; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human