This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors.
This provided further evidence for the engagement of HDAC1 and 2 in genotoxic stress resistance and cell cycle restriction observed upon induction of BCL11B.
Moreover, the recently described Bcl11b-mediated transcriptional repression of P57/KIP2 and p21WAF1 cyclin-dependent kinase inhibitors responsible for cell cycle restriction should lead to effects opposite to the observed cell cycle retardation [13], [21].
In light of the previously described growth-limiting effect of BCL11B in BCL11B-negative HeLa and hematopoietic progenitor cell FDC-P1lines, a tempting hypothesis is that cell cycle restriction causes the reduced percentage of S-phase cells.
Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction.
In sum, we revealed potential mechanisms of Bcl11b-mediated cell cycle restriction which included activation or induction of p18 and p57 cyclin dependent kinase inhibitors, accumulation of p27 p130 and suppression of MYCN oncogene.
However, given the known properties of I-SceI and precedent in the literature [11], [13], it is perhaps more likely that it is the engagement of HR itself that exhibits the observed cell cycle restriction.
Therefore, we were interested in identifying the region of Bcl11b relevant for binding complexes/proteins necessary for the DNA-damage resistance and/or cell cycle restriction following its overexpression.
From these diverse studies, it is generally accepted that over-expression of molecules (cyclins D1, D2, D3, cdk2 or E2F transcription factors) that promote progression through the G1 cell cycle restriction checkpoint can promote DNA synthesis [7], [15] [19]; however, cell cycle progression in mature non-proliferating CM can lead to apoptosis [17], [20] [23].
Since we previously showed that the DNA-damage resistance was accompanied by and presumably associated with cell cycle restriction at the pre-replication phase, we performed the synchronization of the transduced cells at G2/M using nocodazol (Fig. 7b .. DNA staining before nocodazol treatment showed a slightly elevated G0/G1 fraction in BCL11B- ΔC-2 and wild-type BCL11B transduced cells.
