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PMID:20473878
| Citation |
Naik, MU, Pham, NT, Beebe, K, Dai, W and Naik, UP (2011) Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells. Int. J. Cancer 128:587-96 |
|---|---|
| Abstract |
Members of the polo-like kinases (Plk1, Plk2, Plk3 and Plk4) are involved in the regulation of various stages of the cell cycle and have been implicated in cancer progression. Unlike its other family members, the expression of Plk3 remains steady during cell cycle progression, suggesting that its activity may be spatiotemporally regulated. However, the mechanism of regulation of Plk3 activity is not well understood. Here, we show that calcium- and integrin-binding protein 1 (CIB1), a Plk3 interacting protein, is widely expressed in various cancer cell lines. Expression of CIB1 mRNA as well as protein is increased in breast cancer tissue as compared to normal tissue. CIB1 constitutively interacts with Plk3 as determined by both in vitro and in vivo assays. This interaction of CIB1 with Plk3 is independent of intracellular Ca(2+). Furthermore, binding of CIB1 results in inhibition of Plk3 kinase activity both in vitro and in vivo. Interestingly, this inhibition of the Plk3 activity by CIB1 is Ca(2+)-dependent. Taken together, our results suggest that CIB1 is a regulatory subunit of Plk3 and it regulates Plk3 activity in a Ca(2+)-dependent manner. Furthermore, upregulation of CIB1 in cancer cells could thus inhibit Plk3 activity leading to abnormal cell cycle regulation in breast cancer cells. Thus, in addition to Plk3, CIB1 may be a potential biomarker and target for therapeutic intervention of breast cancer. |
| Links |
PubMed PMC2954264 Online version:10.1002/ijc.25388 |
| Keywords |
Base Sequence; Breast Neoplasms/enzymology; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Calcium/metabolism; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Cell Line, Tumor; Female; Humans; Immunohistochemistry; Protein Binding; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA Interference; RNA, Double-Stranded/genetics; RNA, Messenger/genetics; RNA, Small Interfering/genetics; Recombinant Proteins/metabolism; Up-Regulation |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0051592: response to calcium ion |
ECO:0000314: |
P |
Figure 5A-C shows that calcium-bound CIB1 inhibits Plk3 kinase activity and an absence of calcium to bind to CIB1 prevents CIB1 from inhibiting Plk3 kinase activity. |
complete | ||||
| GO:0050685: positive regulation of mRNA processing |
ECO:0000314: |
P |
Figure 1A-C presents results suggesting that CIB1 mRNA expression is upregulated in breast cancer tissue. |
complete | ||||
| GO:0008427: calcium-dependent protein kinase inhibitor activity |
ECO:0000315: |
F |
Figure 5 |
complete | ||||
| GO:0008427: calcium-dependent protein kinase inhibitor activity |
ECO:0000314: |
F |
Figure 5 shows CIB1 inhibits Plk3 kinase activity. |
complete | ||||
| GO:0005886: plasma membrane |
ECO:0000314: |
C |
In figure 2Aii, CIB1 is seen localized along the cell membrane indicating plasma membrane localization as visualized in H & E stains. |
complete | ||||
| GO:0030291: protein serine/threonine kinase inhibitor activity |
ECO:0000314: |
F |
Fig 5 |
complete | ||||
| GO:0005515: protein binding |
ECO:0000314: |
F |
Figure 3A-D shows that CIB1 and Plk3 interact to bind to each other with a high affinity in the cancer cell line T47D. |
complete | ||||
|
part_of |
GO:0005886: plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
|
enables |
GO:0030291: protein serine/threonine kinase inhibitor activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
enables |
GO:0008427: calcium-dependent protein kinase inhibitor activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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