Review on ZFP36L1 (zinc finger protein 36, C3H type-like 1), with data on DNA, on the protein encoded, and where the gene is implicated

Blackshear, PJ

Stumpo, DJ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Gene Section 
Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4)  296 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology                         
                         OPEN ACCESS JOURNAL AT INIST-CNRS 
ZFP36L1 (zinc finger protein 36, C3H type-like 1) 
Deborah J Stumpo, Perry J Blackshear 
Laboratory of Neurobiology, NIEHS MD A2-05, 111 Alexander Drive, Research Triangle Park, NC 27709, 
USA 
Published in Atlas Database: November 2007 
Online updated version: http://AtlasGeneticsOncology.org/Genes/ZFP36L1ID42866ch14q22.html  
DOI: 10.4267/2042/38548 
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence. 
© 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Hugo: ZFP36L1 
Other names: Berg36; BRF1; cMG1; ERF1; TIS11B 
Location: 14q24.1 
Note: The rat clone of ZFP36L1, cMG1, was the first 
cloned member of the tristetraprolin (TTP, TIS11, 
NUP475, GOS24) family of CCCH tandem zinc finger 
proteins. There are 4 mammalian members of this 
family, TTP, ZFP36L1, ZFP36L2 (TIS11D, ERF2, 
BRF2), and ZFP36L3. ZFP36L3 is the only family 
member that is rodent-specific. These proteins have 
been shown to bind (via their conserved tandem zinc
finger domain) directly to class II AU-rich elements 
(ARE) in the 3'-untranslated region (UTR) of mRNA 
leading to deadenylation and destabilization of the
mRNA. 
DNA/RNA 
 
Diagram of the human ZFP36L1 gene. Exons are represented 
by gray boxes; intron by the hatched box. The translation start 
site is indicated by the arrow and the translation stop site by 
the double line. The dark box represents the CCCH tandem 
zinc finger domain. 
Description 
The human ZFP36L1 has 2 exons spanning 5411 bp on 
chromosome 14 (NC_000014.7; NT_026437.11). The 
first exon, which is small (186 bp), is separated from 
the larger second exon (2834 bp) by a 2388 bp intron. 
Transcription 
3022 bp human transcript (NM_004926.2) with 1014 
bp (338 amino acids) of coding region. 
Pseudogene 
None known. 
Protein 
Description 
Human ZFP36L1 is a 338 amino acid protein with a 
predicted molecular weight of 36.3 kDa. 
Expression 
In the adult mouse, expression appears to be 
ubiquitous. Based on northern blots, mRNA expression 
is highest in mouse kidney, spleen, ovary and lung, 
with lower levels of expression in thymus and heart, 
and still lower levels in brain, liver and testis. In the 
embryonic mouse, mRNA was barely detectable at 
embryonic day 7.5 (E7.5), but increased dramatically 
by E9.5 and E10.5. In situ hybridization histochemistry 
demonstrated that there was high level expression in 
the allantois at E8.0, immediately before fusion with 
the chorion. Expression is also seen in mouse 
embryonic stem cells. 
Localisation 
Transfection studies using a GFP-tagged protein have 
shown diffuse cytoplasmic expression. There is good 
evidence that the protein can shuttle between the 
nucleus and the cytoplasm in a CRM1 (nuclear export 
receptor)-dependent, leptomycin B-inhibitable manner. 
Function 
ZFP36L1 is a member of the TTP (ZFP36) family of 
CCCH tandem zinc finger proteins. These proteins 
have been shown to bind to target mRNAs through 
their AU-rich elements present in the 3'-untranslated 
regions of the mRNA. 
The binding of these proteins to mRNA leads to 
deadenylation and destabilization of the mRNA. All 
four family members have been shown to bind directly 
ZFP36L1 (zinc finger protein 36, C3H type-like 1) Stumpo DJ, Blackshear PJ 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4)  297 
to single stranded RNA probes (RNA gel shift assays), 
destabilize target mRNA (co-transfection assays), and
deadenylate ARE-containing RNA probes (cell-free 
deadenylation assays). Physiological target mRNAs 
have been identified for TTP which include tumor 
necrosis factor alpha (TNF), granulocyte-macrophage 
colony stimulating factor (GM-CSF), interleukin-2b 
(IL-2), and immediate early response gene 3 (IER3, 
IEX-1, gly96). 
To date, one physiological target mRNA has been 
identified for ZFP36L1; however, this target mRNA is 
not destabilized by ZFP36L1 (see below). 
Two reports of ZFP36L1 knockout mice have been 
published. In one report, knockout embryos died 
around embryonic day 11 mainly due to failure of 
chorioallantoic fusion. When fusion did occur, there 
was increased apoptosis throughout the neural tube,as 
well as placental failure due to atrophy of the 
trophoblast layers. In a second report, knockout 
embryos also died at mid-gestation and exhibited 
extraembryonic and intraembryonic vascular 
abnormalities and heart defects. In the developing 
placenta, the extraembryonic mesoderm failed to 
invaginate the trophoblast layer. This phenotype was 
associated with an elevated expression of vascular 
endothelial growth factor (VEGF)-A (in the embryo 
and in mouse embryonic fibroblasts). This elevated 
level of expression was not due to increased stability of 
the VEGF-A mRNA, but rather due to enhanced 
association with polyribosomes. 
This is in contrast to a prior report using co-transfection 
studies showing that ZFP36L1 was able to bind to tw 
AU-rich motifs in the 3' UTR of VEGF mRNA that led 
to destabilization of the mRNA. Mouse ZFP36L1 has 
been shown to interact with 14-3-3 proteins in a 
phosphorylation-dependent manner. This interaction 
causes ZFP36L1 to be sequestered in the cytoplasm 
preventing it from regulating mRNA decay. Several 
studies have suggested that ZFP36L1 may function as a 
pro-apoptotic protein. 
Homology 
Four members of the TTP family of CCCH tandem 
zinc finger proteins, TTP (ZFP36), ZFP36L1, ZFP36L2 
and the rodent-specific ZFP36L3, have been identifid. 
They all share a highly conserved tandem zinc finger 
domain. 
Mutations 
Note: Eight polymorphisms have been identified. The 
functional significance of these polymorphisms has not 
been determined. 
1) G change into T at base 644 in the 5' UTR. 
2) AG change into GC at base 706 in the first coding 
region. 
3) G change into A at base 729 in the intron. 
4) C change into CC at base 772 in the intron. 
5) A change into G at base 804 in the intron. 
6) G change into C at base 845 in the intron. 
7) G change into A at base 3685 in the second coding 
region. 
8) C change into A at base 3915 in the second coding 
region. 
Implicated in 
Cisplatin sensitivity in head and neck 
squamous cell carcinoma (HNSCC) 
Note: A common feature in HNSCC is cisplatin 
sensitivity. Microarray analysis identified mouse 
ZFP36L1 to be differentially expressed by cisplatin 
treatment. Cisplatin-sensitive HNSCC cell lines 
expressed elevated levels of ZFP36L1 compared to 
cisplatin-resistant HNSCC cell lines. Downregulation 
of ZFP36L1 (using antisense oligonucleotides) in 
cisplatin-sensitive cell lines made the cells cisplatin-
resistant. Conversely, overexpression of ZFP36L1 
reverted cisplatin-resistant cells to cisplatin-sensitive 
cells. There was an inverse correlation between the 
expression levels of ZFP36L1 and the human inhibitor 
of apoptosis protein-2, cIAP2 (Birc3, baculoviral IAP 
repeat-containing 3). Increased expression of ZFP36L1 
also correlated with increased caspase-3 activity and
increased cisplatin-induced apoptosis. These results 
suggested that expression of ZFP36L1 enhanced 
cisplatin sensitivity in HNSCC cells by reducing cIAP2 
mRNA levels. 
t(8;21) translocation 
Note: The AML1-MTG8 fusion transcription factor 
generated by t(8;21) translocation is thought to affect 
the normal regulation of genes that are needed for 
differentiation and proliferation of hematopoietic 
progenitors leading to acute myelogenous leukemia 
(AML). ZFP36L1 was identified as an up-regulated 
gene in t(8;21) leukemic cells suggesting that it may be 
important to AML1-MTG8-mediated leukemogenesis. 
Human T-lymphotropic virus 1 (HTLV-1) 
Note: ZFP36L1 expression is also up-regulated in 
human T-lymphotropic virus 1(HTLV-1)-infected cells. 
HTLV-1 is associated with adult T-cell 
leukemia/lymphoma and the Tax oncoprotein encoded 
by the 3' region of HTLV-1 has been proposed to 
dysregulate the expression of many genes that are 
important for cell proliferation. The Tax transactivator 
was shown to bind to two ZFP36L1 upstream elements 
(a novel transcription factor-binding site labeled BRF1 
Tax-responsive site or BTRS and a second consensus 
cAMP-responsive site or CRE). 
Various cancers 
Note: Increased expression of ZFP36L1 has been seen 
in several cancers including lymph node (+) primary 
breast tumors and hepatocellular carcinomas. Increased 
ZFP36L1 (zinc finger protein 36, C3H type-like 1) Stumpo DJ, Blackshear PJ 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4)  298 
expression has also been demonstrated in a number of 
the NCI 60 panel of human cancer cell lines. These 
include the mammary gland cancer cell lines BT549, 
MDA-MB-231, and NCI/ADR-RES; ovarian cell lines 
OVCAR-5, OVCAR-8 and SK-OV-3; lung cell line 
NCI-H226; skin cell lines LOXMVI, M14, MALME-
3M, and SK-MEL-2; brain cell lines SF268 and SF295; 
prostate cell line PC-3; kidney cell lines A498, ACHN, 
CAKI-1, SN12C, TK10, and UO31; and colon cell line 
HT29. 
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This article should be referenced as such: 
Stumpo DJ, Blackshear PJ. ZFP36L1 (zinc finger protein 36, 
C3H type-like 1). Atlas Genet Cytogenet Oncol 
Haematol.2008;12(4):296-298. 
 
 
 


ZFP36L1 (zinc finger protein 36, C3H type-like 1)

http://documents.irevues.inist.fr/bitstream/2042/38548/2/11-2007-ZFP36L1ID42866ch14q22.pdf

ZFP36L1 (zinc finger protein 36, C3H type-like 1)

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