NACA (Nascent-Polypeptide-Associated Complex α Subunit) Against Apoptosis in B Lymphoma Cell is Independent of β Subunit (NACB)


  • Weiqi Zeng Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • Min Qi Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • Jianglin Zhang Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • Xiang Chen Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China



NACA, B-cell lymphoma, anti-apoptosis, depletion mutant.


 We found depletion of NACA in two kinds of B lymphoma cell lines, Raji and Kapas, were able to induce apoptosis in this study. We also explored whether depletion of Z² subunit had the same effect, and we were interested in which domain of NACA was potentially responsible to this anti-apoptosis function. Lentivirus-based shRNA was used to deplete endogenous NACA or NACB. Those cells viabilities were measured by Alamar-blueTM assay. Cell apoptosis was identified by molecular markers caspase9 and PARP, as well as cellular markers Annexin V and propidium iodide (PI) staining. NACA mutants were constructed by PCR site-directed mutagenesis and delivered into cells by Lentivirus. Immunofluoresce was used to investigate cellular distribution in 293FT cells. Our results demonstrated that the depletion of NACA, but not NACB, was able to induce apoptosis. Deletion of middle or C-term rather than N-term induced obvious apoptosis. The middle part of NACA was response to bind NACB and form a complex. Without middle part, NACA redistributed into nuclei. We conclude NACA against apoptosis is independent of Z² subunit. C-term of NACA, which is identified as ubiquitin binding domain, and may take important role in anti-apoptosis function.


Zhang Y, Berndt U, Gölz H, et al. NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum. Mol Biol Cell 2012; 23(16): 3027-40.

Lauring B, Wang S, Saka H i, Davis TA, et al. Nascent-polypeptide-associated complex: a bridge between ribosome and cytosol. Cold Spring Harb Symp Quant Biol 1995; 60: 47-56.

Moreau A, Yotov WV, Glorieux FH, St-Arnaud R. Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. Mol Cell Biol 1998; 18(3): 1312-21.

Yotov WV, Moreau A, St-Arnaud R. The alpha chain of the nascent polypeptide-associated complex functions as a transcriptional coactivator. Mol Cell Biol 1998; 18(3): 1303-11.

Stilo R, Liguoro D, di Jeso B, Leonardi A, Vito P. The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function. Biochem Biophys Res Commun 2003; 303(4): 1034-41.

Hotokezaka Y, van Leyen K, Lo EH, et al. Alpha NAC depletion as an initiator of ER stress-induced apoptosis in hypoxia. Cell Death Differ 2009; 16(11): 1505-14.

Kroes RA, Jastrow A, McLone MG, et al. The identification of novel therapeutic targets for the treatment of malignant brain tumors. Cancer Lett 2000; 156(2): 191-8.

Murphy JP, Pinto DM. Temporal proteomic analysis of IGF-1R signalling in MCF-7 breast adenocarcinoma cells. Proteomics 2010; 10(9): 1847-60.

Hämmerle K, Shayan P, Niemeyer CM, Flotho C. Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and ""virtual Northern"" hybridization. Cancer Genet Cytogenet 2003; 142(2): 149-52.

Beatrix B, Sakai H, Wiedmann M. The alpha and beta subunit of the nascent polypeptide-associated complex have distinct functions. J Biol Chem 2000; 275(48): 37838-45.

George R, Walsh P, Beddoe T, Lithgow T. The nascent polypeptide-associated complex (NAC) promotes interaction of ribosomes with the mitochondrial surface in vivo. FEBS Lett 2002; 516(1-3): 213-6.

Akhouayri O, Quélo I, St-Arnaud R. Sequence-specific DNA binding by the alphaNAC coactivator is required for potentiation of c-Jun-dependent transcription of the osteocalcin gene. Mol Cell Biol 2005; 25(9): 3452-60.

Jafarov T, Alexander JW, St-Arnaud R. αNAC interacts with histone deacetylase corepressors to control Myogenin and Osteocalcin gene expression. Biochim Biophys Acta 2012; 1819(11-12): 1208-16.

Spreter T, Pech M, Beatrix B. The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain. J Biol Chem 2005; 280(16): 15849-54.

Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI. Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin. J Proteome Res 2012; 11(2): 796-807.

Kim W, Bennett EJ, Huttlin EL, et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell 2011; 44(2): 325-40.

Thompson SJ, Loftus LT, Ashley MD, Meller R. Ubiquitin-proteasome system as a modulator of cell fate. Curr Opin Pharmacol 2008; 8(1): 90-5.

Calise J, Powell SR. The ubiquitin proteasome system and myocardial ischemia. Am J Physiol Heart Circ Physiol 2013; 304(3): H337-49.

David D, Nair SA, Pillai MR. Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression. Biochim Biophys Acta 2013; 1835(1): 119-28.

Voutsadakis IA. The ubiquitin-proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer. J Biomed Sci 2012; 19: 67.

Chang L, Kamata H, Solinas G, et al. The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 2006; 124(3): 601-13.

Maia S, Haining WN, Ansén S, et al. Gene expression profiling identifies BAX-delta as a novel tumor antigen in acute lymphoblastic leukemia. Cancer Res 2005; 65(21): 10050-8.




How to Cite

Weiqi Zeng, Min Qi, Jianglin Zhang, & Xiang Chen. (2014). NACA (Nascent-Polypeptide-Associated Complex α Subunit) Against Apoptosis in B Lymphoma Cell is Independent of β Subunit (NACB). Journal of Cancer Research Updates, 3(2),  85–92.