Disease relevance of GADD45GIP1

• Expression of CRIF1 is barely detectable in adrenal adenoma and papillary thyroid cancer and much lower than in adjacent normal tissue [1].
• These results suggest that this putative CRIF may be an important component in the development of RA and that regulation of prepro TRH may be highly relevant to the development of other autoimmune diseases that are also exacerbated by low endogenous glucocorticoid levels [2].
• The overexpression of CRIF1 inhibits the androgen-induced proliferation and cell cycle progression of prostate cancer cells [3].

High impact information on GADD45GIP1

• CRIF1 localizes exclusively to the nucleus and colocalizes with Gadd45gamma [1].
• The down-regulation of endogenous CRIF1 by the transfection of the small interfering RNA duplexes resulted in the inactivation of Rb by phosphorylation and decreased the G1 phase cell populations [1].
• CRIF1 mRNA is highly expressed in the thyroid gland, heart, lymph nodes, trachea, and adrenal tissues [1].
• Overexpression of CRIF1 increases the percentage of cells in G1, decreases the percentage of cells in S phase, and suppresses growth in NIH3T3 cells [1].
• The results presented here suggest that CRIF1 is a novel nuclear protein that interacts with Gadd45 and may play a role in negative regulation of cell cycle progression and cell growth [1].

Biological context of GADD45GIP1

• In this study, we demonstrate that CRIF1 acts as a novel coregulator of transactivation of the orphan nuclear receptor Nur77 [4].
• As compared with the wild-type CKBBP2/CRIF1 or nonphosphorylatable mutant CKBBP2(S221A) (in which the serine-221 is replaced by alanine), overexpression of CKBBP2(S221E) in COS7 cells promotes cell proliferation [5].

Associations of GADD45GIP1 with chemical compounds

• CRIF1 possesses intrinsic repressor activities that are not affected by the histone deacetylase inhibitor Trichostatin A [4].
• Transient transfection assays demonstrate that CRIF1 inhibits steroid receptor coactivator-2-mediated Nur77 transactivation, and silencing of endogenous CRIF1 by small interfering RNA relieves this repression [4].
• Phosphoamino acid analysis and mutational analysis indicate that CKII phosphorylates serine at residue 221 within CKBBP2/CRIF1 [5].

Other interactions of GADD45GIP1

• In this study, the two-hybrid system was used to define the subregions of CKIIbeta that are involved in the interaction with L5, L41, topoisomerase IIbeta, SAG/CKBBP1, and unknown proteins, CKBBP2 and CKBBP3 [6].

Analytical, diagnostic and therapeutic context of GADD45GIP1

• In this report, yeast two-hybrid assay and pull-down assay demonstrate that CKBBP2/CRIF1 associates with the beta subunit of CKII in vitro and in vivo [5].

References