GADD45GIP1 (growth arrest and DNA-damage-inducible, gamma interacting protein 1)

2009-03-01   Kentaro Nakayama , Naomi Nakayama , Tian-Li Wang 

Departments of Gynecology-Obstetrics, Oncology, Johns Hopkins Medical Institutions, CRBII, Rm: 306, 1550 Orleans Street, Baltimore, MD 21231, USA




Atlas Image


Gadd45GIP1 gene is encoded by 2 exons located on chromosome 19p13.13. The genomic size is 3078 bp.


mRNA size: 744 bp; coding sequence from 25 bp-693 bp.



The Gadd45GIP1 cDNA has a 669 bp open reading frame encoding a predicted polypeptide of 222 amino acids with a predicted molecular mass of 25 kDa. In vitro translated Gadd45GIP1 cDNA had an apparent size of 28 kDa.
Atlas Image


Using a yeast two-hybrid screen to identify human proteins that interact with Gadd45gamma, Chung et al. (2003) identified Gadd45GIP1 in the screen. Gadd45GIP1 interacts with Gadd45 proteins family, which plays an important role in genomic stability, DNA repair, cell cycle regulation, and apoptosis.


Gadd45GIP1 is widely expressed in normal tissues, including thyroid, heart, lymph node, trachea, adrenal glands, and ovary. Its expression level is lower in neoplastic tissues.


Mainly located at cell nucleus. Contain nuclear localization signal sequence at its C-terminus domain. Gadd45GIP1 co-localized with Gadd45gamma in the nuclei.


Using yeast-two hybrid screen to identify novel proteins that bind to Gadd45 gene family, Chung et al. (2003) has identified CR6-interacting factor 1 (CRIF1 or Gadd45GIP1). Gadd45GIP1 inhibits Cdc2-cyclin B1 kinase and histone H1 kinase activity associated with immunoprecipitated Cdk2-cyclin E. Overexpression of CRIF1 inhibits cell cycle progression at G1/S and suppresses growth in NIH3T3 cells. Gadd45GIP1 interacts with the orphan nuclear receptor, Nur77, and inhibits its transactivation (Park et al., 2005).
To gain more insight in the function of L2 protein of Human Papillomavirus (HPV), Gornemann et al. (2002) performed yeast two hybrid system to isolate putative cellular interaction partners of L2 protein. One of the proteins, designated PLINP, was found to localize in discrete nuclear domains and colocalized with L2. The L2-interacting protein identified may play a role in the viral life cycle and establishment of viral persistence.
Nakayama et al. (2007) identified Gadd45GIP1 as the downstream genes negatively regulated by NAC-1, a member of the BTB/POZ gene family and a transcription repressor, as a gene associated with recurrent ovarian carcinoma after chemotherapy.



There is no report.

Implicated in

Entity name
Various cancers
ovarian cancer, prostate cancer, thyroid cancer
GADD45GIP1 (CRIF1) may play a role in negative regulation of cell cycle progression and cell growth. Down-regulation of GADD45GIP1 (CRIF1) by siRNA induced inactivation of Rb and decreased cells in G1 phase (Chung et al., 2003). Expression of GADD45GIP1 is found to be down-regulated in several cancers including adrenal adenoma, papillary thyroid cancer, and ovarian cancer (Chung et al., 2003; Nakayama et al., 2007). Therefore, altered expression of GADD45GIP1 may contribute to tumorigenesis of some cell types.
More recently, CRIF1 was found to inhibit androgen receptor transactivation through direct physical interaction. Interestingly, CRIF1 represses AR transactivation both by outcompeting AR coactivators and by actively recruiting histone deacetylase (HDAC). Moreover, overexpression of CRIF1 decreases the mRNA level of AR-responsive gene and also inhibits the proliferation and cell cycle progression of prostate cancer cells. The data support the functional role of CRIF1 in prostatic cells (Suh et al., 2008).
Using serial analysis of gene expression, NAC1 was found to be significantly overexpressed in ovarian serous carcinomas (Nakayama et al., 2006). Immunohistochemical analysis of ovarian serous carcinomas localized NAC1 to discrete nuclear bodies, and the level of NAC1 expression was found to be correlated with tumor recurrence. Recently, GADD45GIP1 was identified as a NAC1- regulated gene (Nakayama et al., 2007). NAC-1 knockdown induced Gadd45GIP1 expression transcriptionally in both SKOV3 and HeLa cells; on the other hand, engineered expression of NAC-1 in NAC-1-negative RK3E and HEK293 cells suppressed endogenous Gadd45GIP1 expression. Furthermore, induced Gadd45GIP1 expression resulted in growth arrest in SKOV3 and HeLa cells both in vitro and in vivo, suggesting the tumor suppressor role of Gadd45GIP1.


Pubmed IDLast YearTitleAuthors
127169092003CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle.Chung HK et al
124826592002Interaction of human papillomavirus type 16 L2 with cellular proteins: identification of novel nuclear body-associated proteins.Görnemann J et al
178047172007NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor.Nakayama K et al
154592482005CR6-interacting factor 1 interacts with orphan nuclear receptor Nur77 and inhibits its transactivation.Park KC et al
178852092008CR6-interacting factor 1 represses the transactivation of androgen receptor by direct interaction.Suh JH et al

Other Information

Locus ID:

NCBI: 90480
MIM: 605162
HGNC: 29996
Ensembl: ENSG00000179271


dbSNP: 90480
ClinVar: 90480
TCGA: ENSG00000179271


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Organelle biogenesis and maintenanceREACTOMER-HSA-1852241
Mitochondrial translationREACTOMER-HSA-5368287
Mitochondrial translation initiationREACTOMER-HSA-5368286
Mitochondrial translation elongationREACTOMER-HSA-5389840
Mitochondrial translation terminationREACTOMER-HSA-5419276

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
127169092003CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle.37
204272902010CR6-interacting factor 1 (CRIF1) regulates NF-E2-related factor 2 (NRF2) protein stability by proteasome-mediated degradation.31
178047172007NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor.29
253610832015CR6-interacting factor 1 is a key regulator in Aβ-induced mitochondrial disruption and pathogenesis of Alzheimer's disease.15
178852092008CR6-interacting factor 1 represses the transactivation of androgen receptor by direct interaction.13
258473892015Crif1 Promotes Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells After Irradiation by Modulating the PKA/CREB Signaling Pathway.10
245203162014CRIF1 interacting with CDK2 regulates bone marrow microenvironment-induced G0/G1 arrest of leukemia cells.8
249060052014CRIF1 deficiency induces p66shc-mediated oxidative stress and endothelial activation.7
262104982015Lymphocyte-specific protein tyrosine kinase (Lck) interacts with CR6-interacting factor 1 (CRIF1) in mitochondria to repress oxidative phosphorylation.7
288194522017Co-Activation of PKC-δ by CRIF1 Modulates Oxidative Stress in Bone Marrow Multipotent Mesenchymal Stromal Cells after Irradiation by Phosphorylating NRF2 Ser40.7


Kentaro Nakayama ; Naomi Nakayama ; Tian-Li Wang

GADD45GIP1 (growth arrest and DNA-damage-inducible, gamma interacting protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

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