Jackson was born in the borough of Queens, New York City, and raised in its South Jamaica neighborhood by his mother, Sabrina. A drug dealer, Sabrina raised Jackson until she died in a mysterious fire when Jackson was 8. After his mother's death and his father's departure Jackson was raised by his grandmother. He began boxing at about age 11, and when he was 14 a neighbor opened a boxing gym for local youth. "

In 2002, Eminem heard Jackson's Guess Who's Back? CD, received from Jackson's attorney (who was working with Eminem's manager, Paul Rosenberg). Impressed, Eminem invited Jackson to fly to Los Angeles and introduced him to Dr. Dre. After signing a $1 million record deal, Jackson released No Mercy, No Fear. The mixtape featured one new track, "Wanksta", which appeared on Eminem's 8 Mile soundtrack. Jackson was also signed by Chris Lighty's Violator Management and Sha Money XL's Money Management Group.  Jackson released his debut album, Get Rich or Die Tryin' (described by AllMusic as "probably the most hyped debut album by a rap artist in about a decade"), in February 2003. Rolling Stone noted its "dark synth grooves, buzzy keyboards and a persistently funky bounce", with Jackson complementing the production in "an unflappable, laid-back flow". It debuted at number one on the Billboard 200, selling 872,000 copies in its first four days. The lead single, "In da Club" (noted by The Source for its "blaring horns, funky organs, guitar riffs and sparse hand claps"), set a Billboard record as the most listened-to song in radio history within a week.  Interscope gave Jackson his own label, G-Unit Records, in 2003. He signed Lloyd Banks, Tony Yayo and Young Buck as members of G-Unit, and The Game was later signed in a joint venture with Dr. Dre's Aftermath Entertainment. In March 2005 Jackson's second commercial album, The Massacre, sold 1.14 million copies in its first four days (the highest in an abbreviated sales cycle) and was number one on the Billboard 200 for six weeks. He was the first solo artist with three singles in the Billboard top five in the same week with "Candy Shop", "Disco Inferno" and "How We Do". According to Rolling Stone, "50's secret weapon is his singing voice - the deceptively amateur-sounding tenor croon that he deploys on almost every chorus".  After The Game's departure Jackson signed Olivia and rap veterans Mobb Deep to G-Unit Records, with Spider Loc, M.O.P., 40 Glocc and Young Hot Rod later joining the label, who all eventually departed the label. Jackson expressed an interest in working with rappers other than G-Unit, such as Lil' Scrappy of BME, LL Cool J of Def Jam, Mase of Bad Boy and Freeway of Roc-A-Fella, and recorded with several.

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