Literature DB >> 24136988

The molecular balancing act of p16(INK4a) in cancer and aging.

Kyle M LaPak1, Christin E Burd.   

Abstract

p16(INK4a), located on chromosome 9p21.3, is lost among a cluster of neighboring tumor suppressor genes. Although it is classically known for its capacity to inhibit cyclin-dependent kinase (CDK) activity, p16(INK4a) is not just a one-trick pony. Long-term p16(INK4a) expression pushes cells to enter senescence, an irreversible cell-cycle arrest that precludes the growth of would-be cancer cells but also contributes to cellular aging. Importantly, loss of p16(INK4a) is one of the most frequent events in human tumors and allows precancerous lesions to bypass senescence. Therefore, precise regulation of p16(INK4a) is essential to tissue homeostasis, maintaining a coordinated balance between tumor suppression and aging. This review outlines the molecular pathways critical for proper p16(INK4a) regulation and emphasizes the indispensable functions of p16(INK4a) in cancer, aging, and human physiology that make this gene special.

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Year:  2013        PMID： 24136988      PMCID： PMC3944093          DOI： 10.1158/1541-7786.MCR-13-0350

Source DB:  PubMed          Journal:  Mol Cancer Res        ISSN： 1541-7786            Impact factor:   5.852


  173 in total

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Authors:  W Tong; J W Pollard
Journal:  Mol Cell Biol       Date:  2001-02       Impact factor: 4.272

2.  Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging.

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Journal:  Oncogene       Date:  1997-07-10       Impact factor: 9.867

3.  Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas.

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Journal:  Cancer Res       Date:  1997-08-01       Impact factor: 12.701

4.  Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex.

Authors:  João D Pereira; Stephen N Sansom; James Smith; Marc-Werner Dobenecker; Alexander Tarakhovsky; Frederick J Livesey
Journal:  Proc Natl Acad Sci U S A       Date:  2010-08-23       Impact factor: 11.205

5.  ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways.

Authors:  Y Zhang; Y Xiong; W G Yarbrough
Journal:  Cell       Date:  1998-03-20       Impact factor: 41.582

6.  Jmjd3 inhibits reprogramming by upregulating expression of INK4a/Arf and targeting PHF20 for ubiquitination.

Authors:  Wei Zhao; Qingtian Li; Stephen Ayers; Yifeng Gu; Zhong Shi; Qingyuan Zhu; Yidong Chen; Helen Y Wang; Rong-Fu Wang
Journal:  Cell       Date:  2013-02-28       Impact factor: 41.582

7.  Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.

Authors:  Christin E Burd; Jessica A Sorrentino; Kelly S Clark; David B Darr; Janakiraman Krishnamurthy; Allison M Deal; Nabeel Bardeesy; Diego H Castrillon; David H Beach; Norman E Sharpless
Journal:  Cell       Date:  2013-01-17       Impact factor: 41.582

8.  Activated p53 suppresses the histone methyltransferase EZH2 gene.

Authors:  Xiaohu Tang; Michael Milyavsky; Igor Shats; Neta Erez; Naomi Goldfinger; Varda Rotter
Journal:  Oncogene       Date:  2004-07-29       Impact factor: 9.867

9.  Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation.

Authors:  Sangeeta Dhawan; Shuen-Ing Tschen; Anil Bhushan
Journal:  Genes Dev       Date:  2009-04-15       Impact factor: 11.361

10.  Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A).

Authors:  Cleo L Bishop; Ann-Marie H Bergin; Delphine Fessart; Viola Borgdorff; Elizabeth Hatzimasoura; James C Garbe; Martha R Stampfer; Jim Koh; David H Beach
Journal:  Mol Cell       Date:  2010-11-24       Impact factor: 17.970
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  90 in total

1.  Obesity and p16INK4A Downregulation Activate Breast Adipocytes and Promote Their Protumorigenicity.

Authors:  Huda H Al-Khalaf; Mrad Amir; Falah Al-Mohanna; Asma Tulbah; Adher Al-Sayed; Abdelilah Aboussekhra
Journal:  Mol Cell Biol       Date:  2017-08-11       Impact factor: 4.272

Review 2.  Forging a signature of in vivo senescence.

Authors:  Norman E Sharpless; Charles J Sherr
Journal:  Nat Rev Cancer       Date:  2015-07       Impact factor: 60.716

3.  Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort.

Authors:  Christin E Burd; Juan Peng; Bryon F Laskowski; Jennifer L Hollyfield; Suohui Zhang; Paolo Fadda; Lianbo Yu; Rebecca R Andridge; Janice K Kiecolt-Glaser
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2020-11-13       Impact factor: 6.053

Review 4.  The history and future of targeting cyclin-dependent kinases in cancer therapy.

Authors:  Uzma Asghar; Agnieszka K Witkiewicz; Nicholas C Turner; Erik S Knudsen
Journal:  Nat Rev Drug Discov       Date:  2015-02       Impact factor: 84.694

Review 5.  The role of senescent cells in ageing.

Authors:  Jan M van Deursen
Journal:  Nature       Date:  2014-05-22       Impact factor: 49.962

6.  T Cell Transcriptional Profiling and Immunophenotyping Uncover LAG3 as a Potential Significant Target of Immune Modulation in Multiple Myeloma.

Authors:  Fabienne Lucas; Michael Pennell; Ying Huang; Don M Benson; Yvonne A Efebera; Maria Chaudhry; Tiffany Hughes; Jennifer A Woyach; John C Byrd; Suohui Zhang; Desiree Jones; Xiangnan Guan; Christin E Burd; Ashley E Rosko
Journal:  Biol Blood Marrow Transplant       Date:  2019-08-21       Impact factor: 5.742

7.  mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation.

Authors:  William Damsky; Goran Micevic; Katrina Meeth; Viswanathan Muthusamy; David P Curley; Manjula Santhanakrishnan; Ildiko Erdelyi; James T Platt; Laura Huang; Nicholas Theodosakis; M Raza Zaidi; Scott Tighe; Michael A Davies; David Dankort; Martin McMahon; Glenn Merlino; Nabeel Bardeesy; Marcus Bosenberg
Journal:  Cancer Cell       Date:  2015-01-12       Impact factor: 31.743

8.  Differential impact of RB status on E2F1 reprogramming in human cancer.

Authors:  Christopher McNair; Kexin Xu; Amy C Mandigo; Matteo Benelli; Benjamin Leiby; Daniel Rodrigues; Johan Lindberg; Henrik Gronberg; Mateus Crespo; Bram De Laere; Luc Dirix; Tapio Visakorpi; Fugen Li; Felix Y Feng; Johann de Bono; Francesca Demichelis; Mark A Rubin; Myles Brown; Karen E Knudsen
Journal:  J Clin Invest       Date:  2017-12-04       Impact factor: 14.808

9.  Relationships among folate, alcohol consumption, gene variants in one-carbon metabolism and p16INK4a methylation and expression in healthy breast tissues.

Authors:  Adana A Llanos; Ramona G Dumitrescu; Theodore M Brasky; Zhenhua Liu; Joel B Mason; Catalin Marian; Kepher H Makambi; Scott L Spear; Bhaskar V S Kallakury; Jo L Freudenheim; Peter G Shields
Journal:  Carcinogenesis       Date:  2014-10-24       Impact factor: 4.944

Review 10.  Myeloma in Elderly Patients: When Less Is More and More Is More.

Authors:  Ashley Rosko; Sergio Giralt; Maria-Victoria Mateos; Angela Dispenzieri
Journal:  Am Soc Clin Oncol Educ Book       Date:  2017
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