Kelly to step down from cabinet
Ruth Kelly on her resignation
Transport Secretary Ruth Kelly is to step down from the government at the next cabinet reshuffle.
The mother-of-four told the Labour conference it was time to "step back" from politics and put her family first.
There had been reports she was unhappy with Gordon Brown's leadership, but she described him as a "towering figure".
Mr Brown told the BBC Ms Kelly had informed him of her plans in May, adding: "There are no political issues between Ruth and me."
Mr Brown, who sought to reassert his leadership in his conference speech on Tuesday, denied suggestions more resignations might follow.
Embryology Bill
The reshuffle could come as early as next week, following the Conservative Party conference.
Ms Kelly, whose four children are aged 11 or under, was appointed transport secretary in July 2007 after Mr Brown took over as prime minister.
It is well known that Ruth Kelly was among those most unhappy with the direction of the Labour Party under Gordon Brown
Nick Robinson
BBC political editor
There had been speculation the 40-year-old, a devout Catholic, could leave the government because of her objections to the Human Fertilisation and Embryology Bill.
Bolton West MP Ms Kelly, who previously served as communities secretary and education secretary, is understood to have wanted to resign in May, but to been asked by Mr Brown to stay on until the next reshuffle.
BBC political editor Nick Robinson said Ms Kelly was known to be unhappy with the direction of the government in recent months and, before the prime minister's conference speech on Tuesday, a number of cabinet ministers had been considering resigning with her.
'Determination'
But Ms Kelly told the Labour conference in Manchester: "It's been a tremendous privilege to have worked with both Tony Blair and Gordon Brown, two towering figures in the Labour Party, government and on the world stage.
"But, as well as a frontline politician, I'm also proud to be a mother and a wife. To have been able to hold these jobs, I've relied on the support of my husband and my family.
"So I ask for your understanding when I say that I now owe it to my children and family to take a step back and start putting them first.
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Gordon Brown gives his reaction to Ms Kelly's decision
"If I do not, then I know that this is something I will come to regret deeply."
Ms Kelly, who on Tuesday dismissed suggestions she might leave her job during an interview with BBC Radio Manchester, said: "This was not a decision I took lightly... The past 15 years have been an amazing and, at times, humbling experience."
Visibly moved when talking about her family, she was given a standing ovation by delegates. The Labour conference closed with a speech by deputy leader Harriet Harman.
The prime minister, touring the television and radio studios on Wednesday, paid tribute to Ms Kelly and said her decision - which was first reported on BBC Newsnight - was a personal one and "nothing to do with politics".
He told BBC Radio 4's Today programme: "There are no political issues between Ruth and me."
He also said: "Ruth has been an MP all the time that her children have been growing up...
"This is the decision that every parent faces. It is nothing to do with politics. Sometimes we have got to make decisions that are difficult."
In another interview on BBC 5 Live it was put to Mr Brown that Ms Kelly was "not a big fan of yours".
Mr Brown replied: "She's a very good friend of mine - I think you've got that wrong."
Her said they had worked together when they were both in the Treasury, and said he wished she would stay on in government.
The reshuffle could also see Chief Whip Geoff Hoon made a European commissioner, a No 10 source said.
The MP for Ashfield, a former Member of the European Parliament, is reportedly being lined up to replace Peter Mandelson.
But Mr Hoon told the BBC: "I have not had a discussion specifically relevant to me.
"What would actually be by far the best solution, if it is possible, would be for Peter Mandelson to remain in post. I've certainly had discussions along those lines."
Huge pressure
Mr Brown addressed Labour's annual conference on Tuesday, claiming it was "no time for a novice" to lead the country.
This was seen as an attack on Conservative leader David Cameron and a coded warning to supporters of would-be Labour challenger David Miliband, the foreign secretary.
Mr Brown also sought to reassert his authority by telling party rebels to focus on challenges facing the country, not internal rows.
The prime minister insisted he would steer the country through the current financial crisis.
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He said the Tories could not be trusted to run the economy and vowed Labour would not stop fighting for a "fair society".
He delivered a more personal conference address than normal, preceded by an unusual introduction on to the stage by his wife Sarah.
Mr Brown told Today that "it was her decision to speak", adding: "We work as a team and we are very much people who know that we are in public life."
The Labour conference closed with a speech by deputy leader Harriet Harman.
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