Modulation of midbody derivatives
The number of midbody derivatives in a cell may be modulated by modulating autophagy induced by NBR1. Exemplary methods include modulating the amount or activity of NBR1 in the cell, potentiating or inhibiting binding between NBR1 and Cep55 in the cell, or modulating the amount of Cep55 in the cell. These methods can be used in the treatment of cancers or in methods of reprogramming cells.
1. A method of inducing degradation of a midbody derivative in a cancer cell, the method comprising:
(a) introducing into the cancer cell a nucleic acid that comprises a sequence encoding a Neighbor of BRCA1 (NBR1 ) polypeptide, a composition comprising an NBR1 polypeptide, or an artificial transcription factor that increases transcription of an NBR1 gene,
thereby increasing the amount of NBR1 polypeptide in the cancer cell and inducing degradation of a midbody derivative in the cancer cell.
2. The method of claim 1 , wherein the method comprises introducing into the cancer cell a nucleic acid that comprises a sequence encoding an NBR1 polypeptide.
3. The method of claim 1 , wherein the method comprises introducing into the cancer cell a composition comprising an NBR1 polypeptide or an artificial transcription factor that increases transcription of an NBR1 gene.
4. The method of claim 3 , wherein the composition comprises the NBR1 polypeptide or artificial transcription factor fused with a cell-penetrating peptide, or comprises a liposome.
5. The method of claim 1 , wherein the cancer cell is a cancer stem cell.
6. The method of claim 1 , wherein the cancer cell is in a subject.
7. A method of treating cancer in a subject, the method comprising:
(a) introducing into a cancer cell in the subject a nucleic acid that comprises a sequence encoding a Neighbor of BRCA 1 (NBR1 ) polypeptide, a composition comprising an NBR1 polypeptide, or an artificial transcription factor that increases transcription of an NBR1 gene,
thereby increasing the amount of NBR1 polypeptide and midbody derivative degradation in cancer cells and treating cancer in the subject.
8. The method of claim 7 , wherein the method comprises introducing into the cancer cell a nucleic acid that comprises a sequence encoding an NBR1 polypeptide.
9. The method of claim 7 , wherein the method comprises introducing into the cancer cell a composition comprising an NBR1 polypeptide or an artificial transcription factor that increases transcription of a NBR1 gene.
10. The method of claim 9 , wherein the composition comprises the NBR1 polypeptide or artificial transcription factor fused with a cell-penetrating peptide, or comprises a liposome.
11. The method of claim 7 , wherein the cancer is a breast cancer.
12. The method of claim 7 , wherein the subject is a human.
13. The method of claim 1 , wherein the nucleic acid is a vector.
14. The method of claim 13 , wherein the vector is a viral vector.
15. The method of claim 1 , wherein the cancer cell is a hepatic cancer cell or an adenocarcinoma cancer cell.
16. The method of claim 7 , wherein the nucleic acid is a vector.
17. The method of claim 16 , wherein the vector is a viral vector.
18. The method of claim 7 , wherein the cancer cell is a cancer stem cell.
19. The method of claim 7 , wherein the cancer is hepatic cancer and the cancer cells are hepatic cancer cells.
20. The method of claim 7 , wherein the cancer is an adenocarcinoma and the cancer cells are adenocarcinoma cancer cells.