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Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occurs also in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis.
Gene References into Functions
NRF2 Ser40 phosphorylation was inhibited in Crif1-deficient bone marrow multipotent mesenchymal stromal cells even in the presence of three kinds of PKC agonists, suggesting that CRIF1 might co-activate PKC-delta to phosphorylate NRF2 Ser40. PMID: 28819452
strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-kappaB, all of which were inhibited by SIRT1 overexpression PMID: 29474366
Results demonstrate that knockdown of CRIF1 in HUVECs induces mitochondrial dysfunction and reduces SIRT1 expression along with decreased eNOS phosphorylation and increased eNOS acetylation, thereby promoting endothelial dysfunction. These findings indicate that CRIF1 plays an important role in maintaining mitochondrial and endothelial function through its effects on the SIRT1-eNOS pathway. PMID: 28117598
SNF5 is indispensable for CRIF1-enhanced p53 activity and its function in the suppression of cell cycle arrest in human cancer cells. PMID: 28235567
Study shows that Lck interacts with CRIF1 in the mitochondria and negatively regulates CRIF1-mediated translation of mitochondrion-encoded proteins. PMID: 26210498
our results support a novel function of nuclear Lck in promoting human leukemic T cell survival through interaction with a tumor suppressor, CRIF1 PMID: 25997448
Crif1 is an indispensable regulator of PKAalpha cat that modulates the PKA/CREB signaling pathway to promote adipogenic differentiation of bone marrow mesenchymal stem cells after irradiation PMID: 25847389
The results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Abeta-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. PMID: 25361083
CRIF1 knockdown partially induces endothelial activation via increased ROS production and phosphorylation of p66shc PMID: 24906005
CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor. PMID: 24520316
CKbetaBP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CKbetaBP2/CRIF1. PMID: 24103312
results indicated cell cycle arrest of Jurkat cells in the G0/G1 phase to be induced by primary cultured leukemic BMSCs associated with increased expression of CRIF1 by leukemic cells PMID: 21911160
CRIF1, unlike KEAP1 (which only interacts with N-terminal region of NRF2), physically interacts with both N- and C-terminal regions of NRF2 and promotes NRF2 ubiquitination and subsequent proteasome-mediated NRF2 protein degradation PMID: 20427290
results 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 PMID: 12716909
Phosphorylation of serine-221 in CKBBP2/CRIF1 promotes proliferation of green monkey COS7 cells. PMID: 17069992
NAC-1 contributes to tumor growth and survival by at least inhibiting Gadd45GIP1 expression, which has a tumor suppressor effect in cancer cells. PMID: 17804717
Results suggest that CRIF1 acts as an AR corepressor and may play an important role in the regulation of AR-positive growth of prostate cancer. PMID: 17885209
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Subcellular Location
Mitochondrion. Nucleus.
Protein Families
Mitochondrion-specific ribosomal protein mL64 family
Tissue Specificity
Widely expressed. Highly expressed in the thyroid gland, heart, lymph nodes, trachea and adrenal tissues. Expressed at lower level in liver skeletal muscle, kidney, pancreas, testis, ovary and stomach. Barely detectable in adrenal adenoma and papillary th