In addition, the C1a Asp424Ala mutation (analogous to the αGC Asp514Ala mutation) severely impaired activity and activation.
Once telomere uncapping occurs either endogenously at the end of cellular replicative lifespan or exogenously by reagents and conditions inducing telomere dysfunction, diminished amount and/or impaired activity of TRF2 results in ATM activation.
Yet the human Met carriers also exhibited impaired activity in the prefrontal cortex, a region important for extinguishing fearful associations.
This may result in a non-functional or a protein with abnormal function ultimately resulting in impaired activity in splicing.
Interestingly, this pathway is disturbed in ccRCC [43] and thus may possibly contribute to impaired activity of splicing factors.
Although the tagged protein (Hes7BAP) retains wildtype-like repressor activity in cultured cells (Figure 5A), it shows greatly impaired activity in vivo.
Germ-line mutations in BRCA1 gene increase the susceptibility for the development of familial breast and ovarian cancers, indicating that BRCA1 functions as a tumor suppressor whose impaired activity would contribute to tumorigenesis [1].
Indeed, the THE/THF ratio was low and fell gradually over the generations in this kindred, strongly suggesting impaired activity of renal 11βHSD2, a direct GR target gene [19].
The FL-ΔRBD and FL-RBCC complexes had impaired activity.
Likewise, also NHEJ impaired activity contributes to genomic instability of such a tumor.
