Biallelic Mutations in p16 <sup>INK4a</sup> Confer Resistance to Ras- and Ets-Induced Senescence in Human Diploid Fibroblasts
Authors: Veronique Bataille
Janice Rowe
Sharon Brookes
Thomas J Huot
Julia Newton-Bishop
Patricia Purkis
Eiji Hara
Sarah Drayton
Mike Fried
Gordon Peters
Chandra Gooptu
Mark Harland
Journal: Molecular and Cellular Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: INK4a/ARF; tumor suppressor locus; senescence-like growth arrest; oncogenic Ras; primary cells
Affiliations: Cancer Research UK London Research Institute, Lincoln's Inn Fields, London WC2A 3PX., Cancer Research UK London Research Institute, Lincoln's Inn Fields, London WC2A 3PX, Cancer Research UK Genetic Epidemiology Laboratory, St. James University Hospital, Leeds LS9 7TF, Cancer Research UK Skin Tumour Laboratory, Centre for Cutaneous Research, Royal London School of Medicine, London E1 2AT, University of California at San Francisco Comprehensive Cancer Center, San Francisco, California 94115, Dermatology/Twin Research and Genetic Epidemiology Unit, St. Thomas Hospital, London SE1 7EH, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom

Abstract:  The INK4a/ARF tumor suppressor locus is implicated in the senescence-like growth arrest provoked by oncogenic Ras in primary cells. INK4a and ARF are distinct proteins encoded by transcripts in which a shared exon is decoded in alternative reading frames. Here we analyze dermal fibroblasts (designated Q34) from an individual carrying independent missense mutations in each copy of the common exon. Both mutations alter the amino acid sequence of INK4a and functionally impair the protein, although they do so to different degrees. Only one of the mutations affects the sequence of ARF, causing an apparently innocuous change near its carboxy terminus. Unlike normal human fibroblasts, Q34 cells are not permanently arrested by Ras or its downstream effectors Ets1 and Ets2. Moreover, ectopic Ras enables the cells to grow as anchorage-independent colonies, and in relatively young Q34 cells anchorage independence can be achieved without addition of telomerase or perturbation of the p53 pathway. Whereas ARF plays the principal role in Ras-induced arrest of mouse fibroblasts, our data imply that INK4a assumes this role in human fibroblasts. 

Retracted: No

PubPeer comments:
 The following excerpt is from the discussion section of this publication: ![file] Why do the authors expect the correlation transform to be more efficient in computation time when substituting it with the neighborhood descriptors is reported to have resulted in about 30 times faster optical flow computation in the 2016 CVIU publication by Ali et al. cited here (also, isn t calling the neighborhood descriptors based similarity transform a gradient-based one a stretch)? This extraordinary reported gain is pointed out at the end of this comment at the PubPeer page of the concerned CVIU publication: https: pubpeer.com publications A09D9A3BCBAEF3F84FD4572344DC56#11 **Note:** The first author s (Sharib Ali s) email was already submitted on this page before I wrote this comment on this publication in NeuroImage. It appears that Sharib Ali or someone else has been anticipating some feedback on this publication. Feedback on his numerous other publications can be found on their PubPeer discussion pages (the following search result gives a list of Sharib Ali s publications commented on PubPeer): https: pubpeer.com search?q=sharib+ali **Some highlights of the concerns raised about some of these publications:** Apparently unacknowledged reproduction of some exiting ideas works:  https: pubpeer.com publications A09D9A3BCBAEF3F84FD4572344DC56#9 https: pubpeer.com publications BD8300AE697D7574A34F74DEC40371#2 https: pubpeer.com publications BD8300AE697D7574A34F74DEC40371#6 Some apparent anomalies in results:  https: pubpeer.com publications 52F2E174A4BDA55F91D5B44AC466BD#3 https: pubpeer.com publications BD8300AE697D7574A34F74DEC40371#1 https: pubpeer.com publications A4AA4DAC550DE014EC874D3EAC95F0#3 https: pubpeer.com publications A4AA4DAC550DE014EC874D3EAC95F0#4 https: pubpeer.com publications ECDD9A4E7AC9E09197325E8D60128B#3 Seemingly unfounded propositions:  https: pubpeer.com publications E91AED3C88109FA8014F05257DE26A#6 https: pubpeer.com publications E91AED3C88109FA8014F05257DE26A#5 https: pubpeer.com publications 52F2E174A4BDA55F91D5B44AC466BD#11 ,