Download Gene Section GADD45GIP1 (growth arrest and DNA damage inducible, gamma interacting protein 1)

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GADD45GIP1 (growth arrest and DNA-damageinducible, gamma interacting protein 1)
Kentaro Nakayama, Naomi Nakayama, Tian-Li Wang
Departments of Gynecology-Obstetrics and Oncology, Johns Hopkins Medical Institutions, CRBII, Rm: 306,
1550 Orleans Street, Baltimore, MD 21231, USA (KN, NN, TLW)
Published in Atlas Database: March 2009
Online updated version: http://AtlasGeneticsOncology.org/Genes/GADD45GIP1ID40668ch19p13.html
DOI: 10.4267/2042/44679
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Other names: CKBBP2; CRIF1; MGC4667;
MGC4758; PLINP-1; PLINP1; PRG6; Plinp1
HGNC (Hugo): GADD45GIP1
Location: 19p13.13
Local order: Gene orientation: telomere- 3'
GADD45GIP1 5'- centromere
Description
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.
DNA/RNA
Description
Expression
Gadd45GIP1 gene is encoded by 2 exons located on
chromosome 19p13.13. The genomic size is 3078 bp.
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.
Transcription
mRNA size: 744 bp; coding sequence from 25 bp-693
bp.
Localisation
Protein
Mainly located at cell nucleus. Contain nuclear
localization signal sequence at its C-terminus domain.
Gadd45GIP1 co-localized with Gadd45gamma in the
nuclei.
Note
The Gadd45GIP1 cDNA has a 669 bp open reading
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2)
111
GADD45GIP1 (growth arrest and DNA-damage-inducible, gamma interacting protein 1)
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 expres-sion 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 expres-sion. 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.
Function
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 chemo-therapy.
Mutations
Note
There is no report.
Implicated in
Various cancers
Disease
Ovarian cancer, prostate cancer, thyroid cancer.
Oncogenesis
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
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2)
Nakayama K, et al.
References
Görnemann J, Hofmann TG, Will H, Müller M. Interaction of
human papillomavirus type 16 L2 with cellular proteins:
identification of novel nuclear body-associated proteins.
Virology. 2002 Nov 10;303(1):69-78
Chung HK, Yi YW, Jung NC, Kim D, Suh JM, Kim H, Park KC,
Song JH, Kim DW, Hwang ES, Yoon SH, Bae YS, Kim JM,
112
GADD45GIP1 (growth arrest and DNA-damage-inducible, gamma interacting protein 1)
Bae I, Shong M. CR6-interacting factor 1 interacts with Gadd45
family proteins and modulates the cell cycle. J Biol Chem.
2003 Jul 25;278(30):28079-88
Nakayama K, Nakayama N, Wang TL, Shih IeM. NAC-1
controls cell growth and survival by repressing transcription of
Gadd45GIP1, a candidate tumor suppressor. Cancer Res.
2007 Sep 1;67(17):8058-64
Park KC, Song KH, Chung HK, Kim H, Kim DW, Song JH,
Hwang ES, Jung HS, Park SH, Bae I, Lee IK, Choi HS, Shong
M. CR6-interacting factor 1 interacts with orphan nuclear
receptor Nur77 and inhibits its transactivation. Mol Endocrinol.
2005 Jan;19(1):12-24
Suh JH, Shong M, Choi HS, Lee K. CR6-interacting factor
1 represses the transactivation of androgen receptor by direct
interaction. Mol Endocrinol. 2008 Jan;22(1):33-46
This article should be referenced as such:
Nakayama K, Nakayama N, Davidson B, Sheu JJ, Jinawath N,
Santillan A, Salani R, Bristow RE, Morin PJ, Kurman RJ, Wang
TL, Shih IeM. A BTB/POZ protein, NAC-1, is related to tumor
recurrence and is essential for tumor growth and survival. Proc
Natl Acad Sci U S A. 2006 Dec 5;103(49):18739-44
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2)
Nakayama K, et al.
Nakayama K, Nakayama N, Wang TL. GADD45GIP1 (growth
arrest and DNA-damage-inducible, gamma interacting protein
1). Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2):111113.
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