BCLAF1

Official Full Name

BCL2 associated transcription factor 1

Organism

Homo sapiens

Gene ID

9774

Background

This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Synonyms

BTF; bK211L9.1

Cat.No.	Product Name	Price
CSC-DC001389	Panoply™ Human BCLAF1 Knockdown Stable Cell Line	Inquiry
CSC-SC001389	Panoply™ Human BCLAF1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD01775Z	Human BCLAF1 adenoviral particles	Inquiry
LV06183L	human BCLAF1 (NM_001077441) lentivirus particles	Inquiry
LV06184L	human BCLAF1 (NM_001077440) lentivirus particles	Inquiry
LV06185L	human BCLAF1 (NM_014739) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHG098191	shRNA set against Human BCLAF1(NM_014739.2)	Inquiry
SHG098209	shRNA set against Human BCLAF1(NM_001077440.1)	Inquiry
SHG098227	shRNA set against Mouse Bclaf1(NM_153787.2)	Inquiry
SHG098245	shRNA set against Mouse Bclaf1(NM_001025393.1)	Inquiry
SHG098263	shRNA set against Human BCLAF1(NM_001077441.1)	Inquiry
SHG098281	shRNA set against Mouse Bclaf1(NM_001025392.1)	Inquiry
SHH246098	shRNA set against Human BCLAF1 (NM_014739.2)	Inquiry
SHH246102	shRNA set against Mouse BCLAF1 (NM_153787.2)	Inquiry
SHH246106	shRNA set against Rat BCLAF1 (NM_001047852.2)	Inquiry

Cat.No.	Product Name	Price
CDFH001737	Human BCLAF1 cDNA Clone(NM_001077441.1)	Inquiry
MiUTR1M-02171	BCLAF1 miRNA 3'UTR clone	Inquiry
MiUTR1H-00857	BCLAF1 miRNA 3'UTR clone	Inquiry
MiUTR1H-00856	BCLAF1 miRNA 3'UTR clone	Inquiry
MiUTR1H-00855	BCLAF1 miRNA 3'UTR clone	Inquiry
CDFR003931	Rat Bclaf1 cDNA Clone(NM_001047852.2)	Inquiry
CDFH001738	Human BCLAF1 cDNA Clone(NM_001077440.1)	Inquiry
MiUTR1M-02172	BCLAF1 miRNA 3'UTR clone	Inquiry
MiUTR1M-02173	BCLAF1 miRNA 3'UTR clone	Inquiry
CDFG014538	Mouse Bclaf1 cDNA Clone(NM_001025393.1)	Inquiry
CDCR371938	Rat Bclaf1 ORF Clone(NM_001047852.2)	Inquiry
CDCR034258	Mouse Bclaf1 ORF clone (NM_153787.2)	Inquiry
CDCR034256	Mouse Bclaf1 ORF clone (NM_001025393.1)	Inquiry
CDCR034254	Mouse Bclaf1 ORF clone (NM_001025392.1)	Inquiry
CDCR034252	Human BCLAF1 ORF clone (NM_001077441.1)	Inquiry
CDCR034250	Human BCLAF1 ORF clone (NM_001077440.1)	Inquiry
CDCB193800	Rabbit BCLAF1 ORF clone (XM_008263558.1)	Inquiry

Detailed Information

BCLAF1 was originally identified as a protein that interacts with anti-apoptotic members of the Bcl2 family. Although linked to (and named for its) interaction with BCL2 family members, BCLAF1 does not share structural similarities with these proteins. The presence of an arginine-serine (RS)-rich region near the N-terminus is the most prominent feature of the BCLAF1 open reading frame. Proteins containing the RS domain are typically associated with biogenesis and processing events of the pre-mRNA, such as splicing of the pre-mRNA.

BCLAF1 as a component of ribonucleoprotein (RNP) complexes

Eukaryotic conversion of pre-mRNA into mature mRNA requires the careful coordination of various post-transcriptional events, such as pre-mRNA 5’ capping, splicing, polyadenylation, and mRNA export from the nucleus to the cytoplasm. The step-by-step completion of each stage consists of a dedicated library of molecular factors that are subsequently recruited to the RNA substrate. These factors interact with RNA in RNP complexes that are initially formed during transcription. The protein composition of RNPs is remodeled during each phase of its existence in a dynamic fashion in order to dictate the fate of the contained RNA molecule. Study that examined the composition of human mRNPs using LC-MS/MS discovered the presence of BCLAF1 among newly identified mRNP proteins. The association of BCLAF1 with mRNPs occurred independently of splicing, but was found to be dependent on the presence of CBP80/CBP20, proteins that form the 5’-m7G cap binding complex. A subsequent study identified BCLAF1 in a complex that mediated cyclin D1 message stability together with SNIP1, SkIP, TAP150, and Pinin. SNIP1 was found to be required for the recruitment of the RNA processing factor U2AF65 to cyclin D1 transcripts. Studies also found that BCLAF1 co-precipitates with hnRNP A1, an RNP protein that is bound to cellular RNAs from transcription to translation. Using a prototypical substrate for measuring alternative pre-mRNA splicing, discovered that BCLAF1-deficient fibroblasts have altered levels of spliced transcripts derived from adenovirus E1A pre-mRNA compared to wild-type cells. Although BCLAF1 is bound to general splicing factor U2AF65 in both the absence and presence of DNA damage, only in the presence of DNA damage it associated with phosphorylated BRCA1. These results indicate that the interaction between BCLAF1 and phosphorylated BRCA1 occurs in the DNA damage response and resulted in recruitment of splicing factor U2AF65 to the HPV16 DNA.

Fig. 1. BCLAF1 as a component of ribonucleoprotein (RNP) complexes. (Nilsson K et al.International Journal of Molecular Sciences. 2018.).

BCLAF1 is an important NF-κB signaling transducer and C/EBPβ regulator

BCLAF1 responds to NF-κB activation by upregulation. BCLAF1 contains a putative NF-κB-binding element within its promoter. Both ChIP and reporter assays indicate that NF-κB binds to this region and activates BCLAF1transcription. Kong et al. have also demonstrated that RelA (p65) binds to the BCLAF1 promoter. However, BCLAF1 upregulation by NF-κB may require its activity to reach a certain threshold. Compared with severe and acute DNA damage treatment, mild DNA damage induces senescence. NF-κB activation is low on day 3 of drug treatment, and a relatively full NF-κB activation was achieved on day 7 as indicated by efficient p65 nuclear translocation and dramatic p65 upregulation. Thus, NF-κB signaling during DNA damage-induced senescence appears to be a gradual process and subject to further amplification through upregulation. As reported, Nemo can transmit DDR to NF-κB activation; however, it did not mediate NF-κB upregulation.

Recent studies have linked BCLAF1 to DDR. Lee et al. reported that BCLAF1 interacted with γH2AX and may regulate the Ku70/DNA-PKcs complex in response to DNA damage. Savage et al. demonstrated that BCLAF1 complexes with BRCA1 and influences the radio-sensitivity of cells. Shao et al. have demonstrated that BCLAF1 is involved in persistent and mild DNA damage-induced senescence downstream of NF-κB activation. Depending on the extent of DNA damage, BCLAF1 probably reacts differently. In the acute DNA damage response, BCLAF1 may be recruited to DNA damage foci and facilitates DNA repair. However, under chronic DNA damage conditions, BCLAF1 expression is upregulated in response to NF-κB activation and subsequently amplifies NF-κB downstream signaling to induce cellular senescence.

References:

Nilsson K, Wu C, Schwartz S. Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation. International Journal of Molecular Sciences. 2018;19(6):1735.
Haya Sarras, Solmaz Alizadeh Azami, and J. Peter McPherson. In Search of a Function for BCLAF1. The Scientific World JOURNAL (2010) 10, 1450–1461 ISSN 1537-744X.
Shao A, Sun H, Geng Y, et al. Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence. Cell Death and Differentiation. 2016;23(5):865-875.
Lowe M, Lage J, Paatela E, et al. Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b. Cell reports. 2018;22(8):2118-2132.

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