Liver function controlling agents
The invention provides novel liver function controlling agents and others. The liver function controlling agents of the present invention are useful as preventive/therapeutic agents for diseases such as hepatic dysfunction, hepatitis, liver cancer, liver cirrhosis, etc.
1 . A liver function controlling agent comprising a protein containing an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:31, or a salt thereof.
2 . The agent according to claim 1 , wherein substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3 is an amino acid sequence of 8-21, 54-59, 93-102, 109-116, 118-126, 128-134, 144-149, 162-170, 176-182, 184-189, 193-213, 215-219 and 228-240 in the amino acid sequence represented by SEQ ID NO:1.
3 . The liver function controlling agent comprising a partial peptide of the protein according to claim 1 , or a salt thereof.
4 . The agent according to claim 3 , wherein a partial peptide of the protein according to claim 1 is a peptide comprising an amino acid sequence having an amino acid sequence of 84-240 in the amino acid sequence represented by SEQ ID NO:1.
5 . The liver function controlling agent comprising a DNA containing a DNA having a base sequence encoding the protein according to claim 1 or the partial peptide according to claim 3 .
6 . The agent according to claim 5 , wherein the DNA is a DNA having a base sequence represented by any one of SEQ ID NO:4 to SEQ ID NO:10, or by SEQ ID NO:30.
7 . The liver function controlling agent comprising an antibody to the protein according to claim 1 or the partial peptide according to claim 3 , or to a salt thereof.
8 . A method of screening a liver function controlling agent which comprises using (a) the protein according to claim 1 or the partial peptide according to claim 3 , or a salt thereof, (b) the DNA according to claim 5 , or (c) the antibody according to claim 7 .
9 . A liver function controlling agent comprising a compound obtained using the screening method according to claim 8 , or a salt thereof.
10 . The agent according to claim 1 , 3 , 5 , 7 or 9 , which is a liver function promoting agent.
11 . The agent according to claim 1 , 3 , 5 , 7 or 9 , which is a liver regenerating agent.
12 . The agent according to claim 1 , 3 , 5 , 7 or 9 , which has an action for promoting transfer from the G0 phase to the G1 phase of the cell cycle.
13 . A protein comprising an amino acid sequence represented by SEQ ID NO:31, or a salt thereof.
14 . A DNA bearing a DNA having a base sequence encoding the protein according to claim 13 .
15 . The DNA according to claim 14 having abase sequence represented by SEQ ID NO:30.
16 . A recombinant vector containing the DNA according to claim 15 .
17 . A transformant transformed by the recombinant vector according to claim 16 .
18 . A process of producing the protein or its salt according to claim 13 , which comprises culturing the transformant according to claim 17 , producing, accumulating and collecting the protein according to claim 13 .
19 . An antibody to the protein or its salt according to claim 13 .
20 . A diagnostic agent comprising the DNA according to claim 14 or the antibody according to claim 19 .
21 . An antisense DNA containing a base sequence complementary or substantially complementary to the DNA according to claim 14 and having an action capable of suppressing expression of the DNA.
22 . A method of screening a compound or its salt that accelerates or inhibits the activity of the protein or its salt according to claim 13 , which comprises using the protein or its salt according to claim 13 .
23 . A kit for screening a compound or its salt that accelerates or inhibits the activity of the protein or its salt according to claim 13 , comprising the protein or its salt according to claim 13 .
24 . A compound or its salt that accelerates or inhibits the activity of the protein or its salt according to claim 13 , which is obtainable using the method of screening according to claim 22 or the kit for screening according to claim 23 .
25 . A pharmaceutical composition comprising the compound or its salt according to claim 24 .
26 . The pharmaceutical composition according to claim 25 , which is a liver function controlling agent.
27 . A liver function controlling agent comprising a protein containing an amino acid sequence of 84-240 or 85-240 in the amino acid sequence represented by SEQ ID NO:1.
28 . A method for controlling liver function wherein the method comprises administering to a mammal an effective amount of an isolated protein containing an amino acid sequence represented by SEQ ID NO:1, or a salt thereof.
29 . A method for controlling liver function wherein the method comprises administering to a mammal an effective amount of an isolated protein containing an amino acid sequence of 84-240 or 85-240 in the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof.
30 . The method according to claim 28 or 29 , wherein the controlling of liver function comprises promoting liver function.
31 . The method according to claim 28 or 29 , wherein the controlling of liver function comprises liver regeneration.
32 . The method according to claim 28 or 29 , wherein the controlling of liver function comprises promoting transfer from the G0 phase to the G1 phase of the cell cycle.
33 . A method for controlling liver function wherein the method comprises administering to a mammal an effective amount of an isolated DNA containing a base sequence encoding:
a. a protein containing an amino acid sequence represented by SEQ ID NO: 1; or
b. a protein containing an amino acid sequence of 84-240 or 85-240 in the amino acid sequence represented by SEQ ID NO: 1.
34 . The method according to claim 33 , wherein the DNA is a DNA having a base sequence represented by SEQ ID NO: 4.
35 . A method of screening a test compound or a salt for having a liver function controlling activity, wherein the method comprises comparing:
a. the case in which the protein containing an amino acid sequence represented by SEQ ID NO:1 or the protein containing an amino acid sequence of 84-240 or 85-240 in the amino acid sequence of SEQ ID NO:1 is brought in contact with a liver cell; and
b. the case in which
i. a test compound; and
ii. the protein containing an amino acid sequence represented by SEQ ID NO:1, or the protein containing an amino acid sequence of 84-240 or 85-240 in the amino acid sequence of SEQ ID NO:1,
are brought in contact with a liver cell.