This interac tion is essential to the relocation of TIF1 from euc

This interac tion is essential to the relocation of TIF1 from euchroma tin to heterochromatin that accompanies the differentiation of primitive endoderm like cells. TIF1 is known to interact differentially with HP1 and HP1 in differentiated and non differentiated cells. In non differentiated cells, TIF1 HP1 interaction occurs only in euchromatin and sellectchem selectively involves HP1 and HP1, but not HP1 . In differentiated cells, on the other hand, TIF1 selectively associates with HP1 in hetero chromatin, while TIF1 and HP1 interaction occurs only in euchromatin. These conclusions agree with the reduced level of phosphorylated TIF1 Inhibitors,Modulators,Libraries Ser473 seen here in differ entiated K562 cells. The results herein also revealed that un phosphorylated TIF1 Ser473 interacts more Inhibitors,Modulators,Libraries strongly with HP1 than its phosphorylated coun terpart.

These results further suggest that the phosphorylation of TIF1 Ser473 regulates the differen tial interaction between TIF1 and HP1 . What may be the functional consequences of the phos phorylation of TIF1 Ser473 and its Inhibitors,Modulators,Libraries consequent dissocia tion from HP1s must be addressed. TIF1 interacts with E2F, TRIP Br and CBP p300, and potentiates the co activation of E2F 1 DP 1 by TRIP Br protein. Phos phorylated TIF1 Ser473 may thus be involved in this tri partite functional interaction. This suggestion is supported by our findings that the induction of cyclin A2 is accompanied by an increased level of phosphorylated TIF1 Ser473 and reduced binding of TIF1 to the pro moter. A most provocative question that remains to be answered is whether the Ser473 phosphorylated TIF1 may interact preferentially with transcription factors and serve as a coactivator.

The results also demonstrated that the level of phosphor ylated TIF1 Ser473 peaks at early S and M phases. Two phosphorylation sites other than Ser473, Ser752 and Ser757, were also identified in the course of this investiga tion. Both sites are located in the bromodomain Inhibitors,Modulators,Libraries of TIF1 . The phosphorylation deficient or phosphomimetic mutants of Ser757 did not influence the phosphorylation of Ser473, suggesting that these phosphorylations may be independent events dur ing mitosis. Other phosphorylation sites important for regulating the function of TIF1 have also been identified. The functional consequences of Ser752 and Ser757 phosphorylation remain to be investigated.

PKC mediated TIF1 S473 phosphorylation may be involved in cell cycle progression Numerous examples have demonstrated that PKC is cen trally involved in cell proliferation and differentiation. The activation of PKC uniquely mediates insulin induced proliferation PKC is activated by insulin and interacts with insulin receptor and IRS. Insulin activated PKC interacts Inhibitors,Modulators,Libraries with 3 phosphoinositide selleckchem dependent protein kinase to regulate Protein Kinase B and is responsible for STAT3 activation and keratino cyte proliferation.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>