Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells
Authors: Lianjun Yang
Nan Li
Yizhi Yu
Liang Yuan
Chunmei Wang
Xuetao Cao
Minghui Zhang
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cyclin L2; Transcriptional regulation; Splicing factors; RNA polymerase II; CDK p110 PITSLRE kinase

Abstract:  We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase II. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase II and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis. 

Retracted: No

PubPeer comments:
 Posting for a reader. The Actin panel in Figure 2C of this paper appears to show an unexpected similarity to Actin panels of Figure 5 in another paper by some of the same authors. That paper is: Lili Sui et al., Cloning and functional characterization of human septin 10, a novel member of septin family cloned from dendritic cells, Biochemical and Biophysical Research Communications 304 (2003) 393u2013398, doi:10.1016 S0006-291X(03)00601-6. Pubpeer: https: pubpeer.com publications F52C08F1625C2346AC69324EE35BFD The lanes appear to be shown in a different order and to represent different tissue types or cell lines. Here is an overview screenshot of the similarities between the two figures. ![file] Here is a close-up comparison. ![file] , 
 The same reader pointed out some unexpected similarities between two of the bottom panels in Figure 6C. Some of these more-than-expected similarities are highlighted here. ![file] , 
 Dear Condylocarpon, I think you are asking these question to the wrong person. Could you please ask these questions to the authors, not me? Not sure what you are trying to accomplish here. Thank you, Elisabeth Bik , 
 #2 Dr. Bik, I see that this paper exhibits #FlawCytometry in addition to the Fig. 2C #ShanghaiNorthernBlots (aka SNoBs), as discussed in #1. Not many people know that Observation is a key (if perennially unfashionable) part of the Scientific Method. In that light, might the SNoBs here be worthy of further scientific study? For example, in addition to that Fig. 2C beta-actin SNoB s reuse in another paper, is there not some in-gel duplication going on too? Just asking for a friend. ![image] , 
 #2 One more. ![file] , 
 #5 #5 I think the actin in gels and the similar pictures from facs may not be a severe problem, it could be a coincidence. , 
 #6 *u201dI think the actin in gels and the similar pictures from facs may not be a severe problem, it could be a coincidence.u201d* Coincidence in science tends to be estimated as the probability that the same observation can happen by chance. Here is another Shanghaied gel in Fig. 2C that might also be a coincidence. Or, er, not. It is the gel slice for the lower left RT-PCR beta-actin control. ![image] The legend in the image is duplicated but may not be a severe problem, it could be a coincidence. , 
 #6  the similar pictures from facs may not be a severe problem, it could be a coincidence. The key point with FACS plots is that the constellations of cells compared in #2 and #5 are extreme outliers... the vast majority of cells have fallen into the heavy thunderclouds that dominate each panel. While it is true that one group of very rare outlier measurements in one FACS experiment will form exactly the same pattern as another group in a second experiment, purely by coincidence, it is about as probable that the outliers will form a sequence of letters in the plot, spelling out the message  DRINK PEPSI . , 
 Yet another of these amazing coincidences appears in a Shanghaied RT-PCR gel in Fig. 2B. A pair of cell lines turn out to be remarkably similar. Who knew? It might soon be worth inviting the JBC DIM to consider whether this paper represents a small leap backwards as regards scientific knowledge advancement. But hold your fire for nowu2026 ![image] , 
 In the event that one were to pull up the shadows in the Fig. 8B Bax RT-PCR slice, it would then be revealed to have been Shanghaied in what is increasingly understood to be the modus operandi. Apart from checking for image reuse in other papers, I think we can wind down here. Meaning it is now time to invite the JBC DIM to the conversation. Consider it done. ![image] , 
 2020 Expression of Concern. https: www.jbc.org content 295 26 8875 The publisher of the Journal of Biological Chemistry is issuing an Expression of Concern to inform readers that credible concerns have been raised regarding some of the data and conclusions in the article listed above. The Journal of Biological Chemistry will provide additional information as it becomes available. , 
 Retraction on Jan 1, 2021, published online May 22, 2021 https: www.jbc.org article S0021-9258(21)00555-X fulltext Withdrawal: Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells This article has been withdrawn by the authors except Lianjun Yang who could not be reached. The Journal states that in Fig. 2B, the bands in the CCNL2 gel panel corresponding to CaoV-3 and HeLa were duplicated. In Fig. 2C, the bands in the u03b2-actin panel on the left corresponding to ovary and small intestine were duplicated. The last two lanes in the PITSLRE p110 immunoblot in Fig. 4B were duplicated. The FACS plots in Fig. 6C for CCNL2-AS and mock present duplicated cells. In Fig. 8B, the bands corresponding to CCNL2-AS and mock in the Bax gel panel were duplicated. The withdrawing authors state that they disagree with the Journalu2019s findings. This study was conducted nearly 20 years ago. The age of the work and the lack of availability of data storage makes it difficult for the authors to retrieve the requested raw data. The withdrawing authorsu2019 offer to replace the images in question with those from other experiments under the same conditions was declined by the Journal. The withdrawing authors state that the above issues do not affect the interpretation of the data nor conclusions of this work. This article describes the discovery of novel molecule CCNL2 and characterizes its role in pre-mRNA splicing and tumor cell apoptosis induction. The withdrawing authors state that its function and mechanism have been confirmed by other independent studies. The withdrawing authors have indicated that they plan to resubmit their findings elsewhere for publication. ,