biostudies-literatureTan JLHoward Hughes Medical InstituteNIAID NIH HHSNIEHS NIH HHSNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHSNIGMS NIH HHS34-46https://www.ebi.ac.uk/biostudies/studies/S-EPMC4836061biostudies-literatureUnknown62(1)Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenMolecular cellStress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.PMC4836061R01-HG004361R01CA1404852P01CA120964R01 HL048801P30 CA0065165P30CA006516P50 GM082250T32 GM007324R01CA103846R21 AI107067P01 CA120964R01 CA103846R21AI107067R01 CA140485P30 CA014051R01 AI125104R01-ES023168R01 GM035500Brogie JELaga ACShyh-Chang NSaint-Andre VSantoriello CPandolfi PPHagedorn EJDo BTKim YJYoung RAFogley RDvan Rooijen ETan JLFujinaga KPandell NChang HYZon LIAblain JPrice DHZhou YGreer CBPeterlin BMKim THFlynn RAAsara JMBothmer AClohessy JGYang SWhite RMFan ZPAvagyan SfalseStress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigen2016-01-01T00:00:00Z2016 Apr2026-04-15T11:30:41.409Z2019-03-27T02:11:54ZS-EPMC48360612705878610.1016/j.molcel.2016.03.013